L. Herviou, G. Cavalli, G. Cartron, B. Klein, and J. Moreaux, EZH2 in normal hematopoiesis 628 and hematological malignancies, Oncotarget, vol.7, p.2284, 2016.

B. Barlogie, A. Mitchell, F. Van-rhee, J. Epstein, G. J. Morgan et al., Curing 630 myeloma at last: defining criteria and providing the evidence, Blood, vol.124, pp.3043-631, 2014.

J. G. Lohr, P. Stojanov, S. L. Carter, P. Cruz-gordillo, M. S. Lawrence et al.,

, Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted 634 Therapy, Cancer Cell, vol.25, pp.91-101, 2014.

N. Bolli, H. Avet-loiseau, D. C. Wedge, P. Van-loo, L. B. Alexandrov et al., Heterogeneity of genomic evolution and mutational profiles in multiple myeloma

, Nat Commun, vol.5, 2014.

J. E. Delmore, G. C. Issa, M. E. Lemieux, P. B. Rahl, J. Shi et al., BET 639 Bromodomain Inhibition as a Therapeutic Strategy to Target c-Myc, Cell, vol.640, pp.904-921, 2011.

J. Moreaux, T. Reme, W. Leonard, J. Veyrune, G. Requirand et al.,

, Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase 643 inhibitors, Br J Cancer, vol.109, pp.676-85, 2013.

A. Kalushkova, M. Fryknäs, M. Lemaire, C. Fristedt, P. Agarwal et al.,

, Polycomb Target Genes Are Silenced in Multiple Myeloma, PLoS ONE, vol.646, p.11483, 2010.

P. A. Croonquist and B. Van-ness, The polycomb group protein enhancer of zeste 648 homolog 2 (EZH2) is an oncogene that influences myeloma cell growth and the mutant 649 ras phenotype, Oncogene, vol.24, pp.6269-6280, 2005.

F. Zhao, Y. Chen, R. Li, Y. Liu, L. Wen et al., Triptolide alters histone H3K9 and 651 H3K27 methylation state and induces G0/G1 arrest and caspase-dependent apoptosis 652 in multiple myeloma in vitro, Toxicology, vol.267, pp.70-79, 2010.

P. Agarwal, M. Alzrigat, A. A. Párraga, S. Enroth, U. Singh et al.,

, Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple 655 myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as 656 a potential therapeutic target, Oncotarget, vol.7, p.6809, 2016.

H. Hernando, K. A. Gelato, R. Lesche, G. Beckmann, S. Koehr et al., EZH2 658 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial 659 Tumor Suppressor Genes, Mol Cancer Ther, vol.15, pp.287-98, 2016.

M. Alzrigat, A. A. Párraga, P. Agarwal, H. Zureigat, A. Österborg et al., EZH2 661 inhibition in multiple myeloma downregulates myeloma associated oncogenes and 662 upregulates microRNAs with potential tumor suppressor functions, OncoTarget, vol.663, 2016.

C. Pawlyn, M. D. Bright, A. F. Buros, C. K. Stein, Z. Walters et al.,

, Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and 669 dysregulation of cell cycle control, Blood Cancer J, vol.7, p.549, 2017.

R. T. Kurmasheva, M. Sammons, E. Favours, J. Wu, D. Kurmashev et al., Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by 672 the Pediatric Preclinical Testing Program: Kurmasheva et al. Pediatr Blood Cancer, vol.673, 2016.

J. Moreaux, B. Klein, R. Bataille, G. Descamps, S. Maiga et al., A high-risk 675 signature for patients with multiple myeloma established from the molecular 676 classification of human myeloma cell lines, Haematologica, vol.96, pp.574-82, 2011.

D. Hose, T. Reme, T. Hielscher, J. Moreaux, T. Messner et al.,

D. Hose, T. Rème, T. Meissner, J. Moreaux, A. Seckinger et al., Proliferation is a central independent prognostic factor and target for personalized and 679 risk-adapted treatment in multiple myeloma, Haematologica, vol.96, pp.4331-4340, 2009.

B. Barlogie, M. Pineda-roman, M. Zangari, F. Van-rhee, E. Anaissie et al., Hoering A, 687 et al. VTD combination therapy with bortezomib-thalidomide-dexamethasone is highly 688 effective in advanced and refractory multiple myeloma, Leukemia, vol.685, pp.1419-1446, 2006.

G. Mulligan, C. Mitsiades, B. Bryant, F. Zhan, W. J. Chng et al., Gene 690 expression profiling and correlation with outcome in clinical trials of the proteasome 691 inhibitor bortezomib, Bioinformatics, vol.109, pp.1-697, 2004.

G. Yu and Q. He, ReactomePA: an R/Bioconductor package for reactome pathway 701 analysis and visualization, Mol BioSyst, vol.12, pp.477-486, 2016.

A. Kassambara, T. Rème, J. M. Fest, T. Hose, D. Tarte et al.,

, GenomicScape: An Easy-to-Use Web Tool for Gene Expression Data Analysis

R. Küffner, N. Zach, R. Norel, J. Hawe, D. Schoenfeld et al., Crowdsourced 707 analysis of clinical trial data to predict amyotrophic lateral sclerosis progression, Application to Investigate the Molecular Events in the Differentiation of B Cells into 705 Plasma Cells, vol.11, pp.51-58, 2014.

J. Moreaux, T. Reme, W. Leonard, J. Veyrune, G. Requirand et al., 710 Development of Gene Expression-Based Score to Predict Sensitivity of Multiple 711

, Myeloma Cells to DNA Methylation Inhibitors, Mol Cancer Ther, vol.11, pp.2685-92, 2012.

M. J. Aryee, A. E. Jaffe, H. Corrada-bravo, C. Ladd-acosta, A. P. Feinberg et al., , p.714

, Infinium DNA methylation microarrays, Bioinformatics, vol.30, pp.1363-1372, 2014.

M. Lawrence, W. Huber, H. Pagès, P. Aboyoun, M. Carlson et al.,

, Software for Computing and Annotating Genomic Ranges, PLoS Comput Biol, vol.9, 2013.

T. Hothorn and B. Lausen, On the exact distribution of maximally selected rank 719 statistics, Comput Stat Data Anal, vol.43, pp.121-137, 2003.

T. E. Cummin, S. Araf, M. Du, S. Barrans, M. A. Bentley et al., PROGNOSTIC 721 SIGNIFICANCE AND CORRELATION TO GENE EXPRESSION PROFILE OF EZH2 722 MUTATIONS IN DIFFUSE LARGE B-CELL LYMPHOMA (DLBL) IN 2 LARGE 723 PROSPECTIVE STUDIES, Hematol Oncol, vol.35, pp.158-159, 2017.

A. A. Guirguis, B. L. Ebert, C. C. Bjorklund, L. Lu, J. Kang et al., Rate 727 of CRL4CRBN substrate Ikaros and Aiolos degradation underlies differential activity of 728 lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and 729 IRF4, Curr Opin Cell Biol, vol.37, p.354, 2015.

T. Ezponda, D. Dupéré-richer, C. M. Will, E. C. Small, N. Varghese et al.,

S. Garapaty-rao, C. Nasveschuk, A. Gagnon, E. Y. Chan, P. Sandy et al., 734 Identification of EZH2 and EZH1 Small Molecule Inhibitors with Selective Impact on 735 Diffuse Large B Cell Lymphoma Cell Growth, Chem Biol, vol.21, pp.1329-1368, 2013.

E. Viré, C. Brenner, R. Deplus, L. Blanchon, M. Fraga et al., The Polycomb 737 group protein EZH2 directly controls DNA methylation, Nature, vol.439, pp.871-875, 2005.

M. Toyota, C. Ho, M. Ohe-toyota, S. B. Baylin, and J. Issa, Inactivation of CACNA1G, 739 a T-type calcium channel gene, by aberrant methylation of its 5? CpG island in human 740 tumors, Cancer Res, vol.59, pp.4535-4541, 1999.

Y. Cha, K. Kim, S. Han, Y. Y. Rhee, J. M. Bae et al., Adverse prognostic 742 impact of the CpG island methylator phenotype in metastatic colorectal cancer, Br J 743 Cancer, vol.115, pp.164-71, 2016.

T. Ohkubo, T-type voltage-activated calcium channel Cav3.1, but not Cav3.2, is 745 involved in the inhibition of proliferation and apoptosis in MCF-7 human breast cancer 746 cells, Int J Oncol, 2012.

Y. Cohen, E. Merhavi-shoham, R. B. Avraham, S. Frenkel, J. Pe'er et al.,

C. M. Bailey, D. E. Abbott, N. V. Margaryan, Z. Khalkhali-ellis, and M. Hendrix, Interferon 751 Regulatory Factor 6 Promotes Cell Cycle Arrest and Is Regulated by the Proteasome 752 in a Cell Cycle-Dependent Manner, Mol Cell Biol, vol.86, pp.2235-2278, 2008.

T. Zengin, B. Ekinci, C. Kucukkose, O. Yalcin-ozuysal, L. A. Mostovich et al., IRF6 Is Involved in the 754 Regulation of Cell Proliferation and Transformation in MCF10A Cells Downstream of 755 Notch Signaling, Cell Adhes Migr, vol.10, pp.395-401, 2011.

V. N. Senchenko, N. P. Kisseljova, T. A. Ivanova, A. A. Dmitriev, and G. S. Krasnov, , p.760

A. V. Kudryavtseva, Novel tumor suppressor candidates on chromosome 3 761 revealed by NotI-microarrays in cervical cancer, Epigenetics, vol.8, pp.409-429, 2013.

, Oncotarget, vol.6, p.31493, 2015.

M. Mumby, PP2A: Unveiling a Reluctant Tumor Suppressor, Cell, vol.130, pp.21-25, 2007.

E. G. Bluemn, E. S. Spencer, B. Mecham, R. R. Gordon, I. Coleman et al., PPP2R2C Loss Promotes Castration-Resistance and Is Associated with, p.768

, Prostate Cancer-Specific Mortality. Mol Cancer Res, vol.11, pp.568-78, 2013.

D. Bi, H. Ning, S. Liu, X. Que, and K. Ding, miR-1301 promotes prostate cancer 770 proliferation through directly targeting PPP2R2C, Biomed Pharmacother, vol.81, p.30, 2016.

. Wu-a-h, Y. Huang, L. Zhang, G. Tian, Q. Liao et al., MiR-572 prompted cell 773 proliferation of human ovarian cancer cells by suppressing PPP2R2C expression

, Biomed Pharmacother, vol.77, pp.92-99, 2016.

Y. Fan, L. Chen, J. Wang, Q. Yao, and J. Wan, Over expression of PPP2R2C inhibits 776 human glioma cells growth through the suppression of mTOR pathway, FEBS Lett, vol.777, pp.3892-3899, 2013.

Y. Sugita, C. Ohwada, T. Kawaguchi, T. Muto, S. Tsukamoto et al.,

, Prognostic impact of serum soluble LR11 in newly diagnosed diffuse large B-cell 780 lymphoma: A multicenter prospective analysis, Clin Chim Acta, vol.463, pp.47-52, 2016.

P. Krzeminski, L. A. Corchete, J. L. García, L. López-corral, E. Fermiñán et al., Integrative analysis of DNA copy number, DNA methylation and gene expression in 783 multiple myeloma reveals alterations related to relapse, Oncotarget. 2016, vol.784

, Carcinogenesis, vol.28, pp.2096-104, 2007.

C. Wu, Migfilin and its binding partners: from cell biology to human diseases, J Cell 789 Sci, vol.118, pp.659-64, 2005.

J. Fan, Y. Ou, C. Wu, C. Yu, Y. Song et al., Migfilin sensitizes cisplatin-induced 791 apoptosis in human glioma cells in vitro, Acta Pharmacol Sin, vol.33, pp.1301-1310, 2012.

V. Gkretsi, V. Papanikolaou, L. C. Zacharia, E. Athanassiou, C. Wu et al., Mitogen-793 inducible Gene-2 (MIG2) and migfilin expression is reduced in samples of human 794 breast cancer, Anticancer Res, vol.33, pp.1977-1981, 2013.

H. Ma, L. Wang, T. Zhang, H. Shen, and J. Du, Loss of ?-arrestin1 expression predicts 796 unfavorable prognosis for non-small cell lung cancer patients, Tumor Biol, vol.797, pp.1341-1348, 2016.

H. Shen, L. Wang, J. Zhang, W. Dong, T. Zhang et al., ARRB1 enhances the 799 chemosensitivity of lung cancer through the mediation of DNA damage response

A. Kumar, A. Bhanja, J. Bhattacharyya, and B. G. Jaganathan, Multiple roles of CD90 in 802 cancer, Tumor Biol, vol.801, issue.59, pp.11611-11633, 2016.

M. Cavo, S. V. Rajkumar, A. Palumbo, P. Moreau, R. Orlowski et al., 804 International Myeloma Working Group consensus approach to the treatment of 805 multiple myeloma patients who are candidates for autologous stem cell 806 transplantation, Blood, vol.117, pp.6063-73, 2011.

K. C. Anderson, A. The-39th-david, A. Karnofsky-lecture-;-méndez, L. Mendoza, M. Boi et al., Bench-to-Bedside Translation 808 of Targeted Therapies in Multiple Myeloma, PLOS Comput Biol, vol.30, pp.1223-1231, 2012.

J. Alinikula, K. Nera, S. Junttila, O. Lassila, Y. Inagaki et al., PAX5 816 tyrosine phosphorylation by SYK co-operatively functions with its serine 817 phosphorylation to cancel the PAX5-dependent repression of BLIMP1: A mechanism 818 for antigen-triggered plasma cell differentiation, Biochem Biophys Res Commun, vol.41, pp.176-81, 2011.

G. Yao, Modelling mammalian cellular quiescence. Interface Focus, vol.821, pp.20130074-20130074, 2014.

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G. Felsenfeld, A Brief History of Epigenetics, Cold Spring Harb. Perspect. Biol, vol.6, issue.1, pp.18200-018200, 2014.

N. A. Villota-salazar, A. Mendoza-mendoza, and J. M. González-prieto, Epigenetics: from the past to the present. Front, Life Sci, vol.9, issue.4, pp.347-370, 2016.

A. D. Goldberg, C. D. Allis, and E. Bernstein, Epigenetics: A Landscape Takes Shape, Cell, vol.128, issue.4, pp.635-638, 2007.

E. G. Toraño, M. G. García, J. L. Fernández-morera, P. Niño-garcía, and A. F. Fernández, The Impact of External Factors on the Epigenome: In Utero and over Lifetime, BioMed Res. Int, vol.2016, pp.1-17, 2016.

M. S. Ebert and P. A. Sharp, Roles for MicroRNAs in Conferring Robustness to Biological Processes, Cell, vol.149, issue.3, pp.515-524, 2012.

D. Hanahan and R. A. Weinberg, Hallmarks of Cancer: The Next Generation, Cell, vol.144, issue.5, pp.646-674, 2011.

Y. Peng and C. M. Croce, The role of MicroRNAs in human cancer, Signal Transduct. Target. Ther, vol.1, p.15004, 2016.

H. Suzuki, R. Maruyama, E. Yamamoto, and M. Kai, DNA methylation and microRNA dysregulation in cancer, Mol. Oncol, vol.6, issue.6, pp.567-578, 2012.

A. Ramassone, S. Pagotto, A. Veronese, and R. Visone, Epigenetics and MicroRNAs in Cancer, Int. J. Mol. Sci, vol.19, issue.2, p.459, 2018.

W. Zhou, H. Q. Dinh, and Z. Ramjan, DNA methylation loss in late-replicating domains is linked to mitotic cell division, Nat. Genet, 2018.

X. Wu and Y. Zhang, TET-mediated active DNA demethylation: mechanism, function and beyond, Nat. Rev. Genet, vol.18, issue.9, pp.517-534, 2017.

M. Cogné, Activation-induced deaminase in B lymphocyte maturation and beyond, Biomed. J, vol.36, issue.6, p.259, 2013.

P. M. Dominguez and R. Shaknovich, Epigenetic Function of Activation-Induced Cytidine Deaminase and Its Link to, Lymphomagenesis. Front. Immunol, vol.5, 2014.

X. Yang, H. Han, D. Carvalho, and D. D. , Gene Body Methylation Can Alter Gene Expression and Is a Therapeutic Target in Cancer, Cancer Cell, vol.26, issue.4, pp.577-590, 2014.

A. Breiling and F. Lyko, Epigenetic regulatory functions of DNA modifications: 5-methylcytosine and beyond, Epigenetics Chromatin, vol.8, issue.1, 2015.

D. Shi, A. I. Tang, J. Yang, and W. , New Insights into 5hmC DNA Modification: Generation, Distribution and Function, Front. Genet, vol.8, 2017.

G. Liang and D. J. Weisenberger, DNA methylation aberrancies as a guide for surveillance and treatment of human cancers, Epigenetics, vol.12, issue.6, pp.416-432, 2017.

W. Zhang and J. Xu, DNA methyltransferases and their roles in tumorigenesis, Biomark. Res, vol.5, 2017.

K. D. Rasmussen and K. Helin, Role of TET enzymes in DNA methylation, development, and cancer, Genes Dev, vol.30, issue.7, pp.733-750, 2016.

A. Pombo and N. Dillon, Three-dimensional genome architecture: players and mechanisms, Nat. Rev. Mol. Cell Biol, vol.16, issue.4, pp.245-257, 2015.

B. Bonev and G. Cavalli, Organization and function of the 3D genome, Nat. Rev. Genet, vol.17, issue.11, pp.661-678, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01386805

J. Fraser, C. Ferrai, and A. M. Chiariello, Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation, Mol. Syst. Biol, vol.11, issue.12, pp.852-852, 2015.

P. Szalaj and D. Plewczynski, Three-dimensional organization and dynamics of the genome, Cell Biol. Toxicol, 2018.

H. K. Norton and J. E. Phillips-cremins, Crossed wires: 3D genome misfolding in human disease, J. Cell Biol, vol.216, issue.11, p.3441, 2017.

B. P. Madakashira and K. C. Sadler, DNA Methylation, Nuclear Organization, and Cancer, Front. Genet, vol.8, 2017.

J. Achinger-kawecka, P. C. Taberlay, and S. J. Clark, Alterations in Three-Dimensional Organization of the Cancer Genome and Epigenome, Cold Spring Harb. Symp. Quant. Biol, vol.81, pp.41-51, 2016.

P. C. Taberlay, J. Achinger-kawecka, and A. Lun, Three-dimensional disorganization of the cancer genome occurs coincident with long-range genetic and epigenetic alterations, Genome Res, vol.26, issue.6, pp.719-731, 2016.

!. #&amp;%!,

Z. A. Gurard-levin and G. Almouzni, Histone modifications and a choice of variant: a language that helps the genome express itself, vol.6, 1000.

S. Henikoff and M. M. Smith, Histone Variants and Epigenetics, Cold Spring Harb. Perspect. Biol, vol.7, issue.1, p.19364, 2015.

M. Buschbeck and S. B. Hake, Variants of core histones and their roles in cell fate decisions, development and cancer, Nat. Rev. Mol. Cell Biol, vol.18, issue.5, pp.299-314, 2017.

Y. Zhao and B. A. Garcia, Comprehensive Catalog of Currently Documented Histone Modifications, Cold Spring Harb. Perspect. Biol, vol.7, issue.9, p.25064, 2015.

X. Zhang, Y. Huang, and X. Shi, Emerging roles of lysine methylation on non-histone proteins, Cell. Mol. Life Sci, vol.72, issue.22, pp.4257-4272, 2015.

T. Kouzarides, SnapShot: Histone-Modifying Enzymes, Cell, vol.131, issue.4, pp.822-822, 2007.

B. D. Strahl and C. D. Allis, The language of covalent histone modi®cations, vol.403, p.5, 2000.

K. Prakash and D. Fournier, Evidence for the implication of the histone code in building the genome structure, Biosystems, vol.164, pp.49-59, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01787125

C. Cayrou, B. Ballester, and I. Peiffer, The chromatin environment shapes DNA replication origin organization and defines origin classes, Genome Res, vol.25, issue.12, pp.1873-1885, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02154106

M. Mohan, H. Herz, and A. Shilatifard, SnapShot: Histone Lysine Methylase Complexes, Cell, vol.149, issue.2, pp.498-498, 2012.

F. Lan and Y. Shi, Histone H3.3 and cancer: A potential reader connection, Proc. Natl. Acad. Sci, vol.112, issue.22, pp.6814-6819, 2015.
URL : https://hal.archives-ouvertes.fr/hal-02154247

E. S. Chrun, F. Modolo, and F. I. Daniel, Histone modifications: A review about the presence of this epigenetic phenomenon in carcinogenesis, Pathol. -Res. Pract, vol.213, issue.11, pp.1329-1339, 2017.

H. Ü. Kaniskan, M. L. Martini, and J. J. , Inhibitors of Protein Methyltransferases and Demethylases, Chem. Rev, vol.118, issue.3, pp.989-1068, 2018.

L. Morera, M. Lübbert, and M. Jung, Targeting histone methyltransferases and demethylases in clinical trials for cancer therapy, Clin. Epigenetics, vol.8, issue.1, 2016.

P. Filippakopoulos and S. Knapp, Targeting bromodomains: epigenetic readers of lysine acetylation, Nat. Rev. Drug Discov, vol.13, issue.5, pp.337-356, 2014.

J. J. Pesavento, H. Yang, N. L. Kelleher, and C. A. Mizzen, Certain and Progressive Methylation of Histone H4 at Lysine 20 during the Cell Cycle, Mol. Cell. Biol, vol.28, issue.1, pp.468-486, 2008.

J. Brustel, M. Tardat, O. Kirsh, C. Grimaud, and E. Julien, Coupling mitosis to DNA replication: The emerging role of the histone H4-lysine 20 methyltransferase PR-Set7, Trends Cell Biol, vol.21, issue.8, pp.452-460, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02193483

N. Zheng, X. Dai, Z. Wang, and W. Wei, A new layer of degradation mechanism for PR-Set7/Set8 during cell cycle, Cell Cycle, pp.1-6, 2016.

S. Wu and J. C. Rice, A new regulator of the cell cycle: The PR-Set7 histone methyltransferase, Cell Cycle, vol.10, issue.1, pp.68-72, 2011.

S. Wu, W. Wang, and X. Kong, Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression, Genes Dev, vol.24, issue.22, pp.2531-2542, 2010.

Y. Yin, V. C. Yu, G. Zhu, and D. C. Chang, SET8 plays a role in controlling G 1 /S transition by blocking lysine acetylation in histone through binding to H4 N-terminal tail, Cell Cycle, vol.7, issue.10, pp.1423-1432, 2008.

A. Zouaz, C. Fernando, and Y. Perez, Cell-cycle regulation of non-enzymatic functions of the Drosophila methyltransferase PR-Set7, Nucleic Acids Res, vol.46, issue.6, pp.2834-2849, 2018.
URL : https://hal.archives-ouvertes.fr/hal-02292938

T. Abbas, E. Shibata, and J. Park, CRL4Cdt2 Regulates Cell Proliferation and Histone Gene Expression by Targeting PR-Set7/Set8 for Degradation, Mol. Cell, vol.40, issue.1, pp.9-21, 2010.

R. C. Centore, C. G. Havens, and A. L. Manning, CRL4Cdt2-Mediated Destruction of the Histone Methyltransferase Set8 Prevents Premature Chromatin Compaction in S Phase, Mol. Cell, vol.40, issue.1, pp.22-33, 2010.

S. Jørgensen, M. Eskildsen, and K. Fugger, SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation, J. Cell Biol, vol.192, issue.1, pp.43-54, 2011.

S. Jorgensen, G. Schotta, and C. S. Sorensen, Histone H4 Lysine 20 methylation: key player in epigenetic regulation of genomic integrity, Nucleic Acids Res, vol.41, issue.5, pp.2797-2806, 2013.

!. #&amp;&amp;!,

M. Takawa, H. Cho, and S. Hayami, Histone Lysine Methyltransferase SETD8 Promotes Carcinogenesis by Deregulating PCNA Expression, Cancer Res, vol.72, issue.13, pp.3217-3227, 2012.

Y. Li, R. L. Armstrong, R. J. Duronio, and D. M. Macalpine, Methylation of histone H4 lysine 20 by PR-Set7 ensures the integrity of late replicating sequence domains in Drosophila, Nucleic Acids Res, p.333, 2016.

S. I. Houston, K. J. Mcmanus, and M. M. Adams, Catalytic Function of the PR-Set7 Histone H4 Lysine 20 Monomethyltransferase Is Essential for Mitotic Entry and Genomic Stability, J. Biol. Chem, vol.283, issue.28, pp.19478-19488, 2008.

M. Tardat, J. Brustel, and O. Kirsh, The histone H4 Lys 20 methyltransferase PR-Set7 regulates replication origins in mammalian cells, Nat. Cell Biol, vol.12, issue.11, pp.1086-1093, 2010.
URL : https://hal.archives-ouvertes.fr/hal-02193626

M. Tardat, R. Murr, Z. Herceg, C. Sardet, and E. Julien, PR-Set7-dependent lysine methylation ensures genome replication and stability through S phase, J. Cell Biol, vol.179, issue.7, pp.1413-1426, 2007.

S. Jørgensen, I. Elvers, and M. B. Trelle, The histone methyltransferase SET8 is required for S-phase progression, J. Cell Biol, vol.179, issue.7, pp.1337-1345, 2007.

L. M. Congdon, S. I. Houston, C. S. Veerappan, T. M. Spektor, and J. C. Rice, PR-Set7-mediated monomethylation of histone H4 lysine 20 at specific genomic regions induces transcriptional repression, J. Cell. Biochem, vol.110, issue.3, pp.609-619, 2010.

Z. Li, F. Nie, S. Wang, and L. Li, Histone H4 Lys 20 monomethylation by histone methylase SET8 mediates Wnt target gene activation, Proc. Natl. Acad. Sci, vol.108, issue.8, pp.3116-3123, 2011.

T. M. Spektor, L. M. Congdon, C. S. Veerappan, and J. C. Rice, The UBC9 E2 SUMO Conjugating Enzyme Binds the PR-Set7 Histone Methyltransferase to Facilitate Target Gene Repression, PLoS ONE, vol.6, issue.7, p.22785, 2011.

P. Kapoor-vazirani and P. M. Vertino, A Dual Role for the Histone Methyltransferase PR-SET7/SETD8 and Histone H4 Lysine 20 Monomethylation in the Local Regulation of RNA Polymerase II Pausing, J. Biol. Chem, vol.289, issue.11, pp.7425-7437, 2014.

K. Wakabayashi, M. Okamura, and S. Tsutsumi, The Peroxisome Proliferator-Activated Receptor /Retinoid X Receptor Heterodimer Targets the Histone Modification Enzyme PR-Set7/Setd8 Gene and Regulates Adipogenesis through a Positive Feedback Loop, Mol. Cell. Biol, vol.29, issue.13, pp.3544-3555, 2009.

X. Shi, I. Kachirskaia, and H. Yamaguchi, Modulation of p53 Function by SET8-Mediated Methylation at Lysine 382, Mol. Cell, vol.27, issue.4, pp.636-646, 2007.

L. E. West, S. Roy, and K. Lachmi-weiner, The MBT Repeats of L3MBTL1 Link SET8-mediated p53 Methylation at Lysine 382 to Target Gene Repression, J. Biol. Chem, vol.285, issue.48, pp.37725-37732, 2010.

N. Kalakonda, W. Fischle, and P. Boccuni, Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1, Oncogene, vol.27, issue.31, p.4293, 2008.

G. K. Dhami, H. Liu, and M. Galka, Dynamic Methylation of Numb by Set8 Regulates Its Binding to p53 and Apoptosis, Mol. Cell, vol.50, issue.4, pp.565-576, 2013.

S. Weirich, D. Kusevic, S. Kudithipudi, and A. Jeltsch, Investigation of the methylation of Numb by the SET8 protein lysine methyltransferase, Sci. Rep, vol.5, issue.1, 2015.

I. Driskell, H. Oda, and S. Blanco, The histone methyltransferase Setd8 acts in concert with c-Myc and is required to maintain skin, EMBO J, vol.31, issue.3, pp.616-629, 2012.

V. Veschi and C. J. Thiele, High-SETD8 inactivates p53 in neuroblastoma, Oncoscience, vol.4, p.21, 2017.

H. Tanaka, S. Takebayashi, and A. Sakamoto, The SETD8/PR-Set7 Methyltransferase Functions as a Barrier to Prevent Senescence-Associated Metabolic Remodeling, Cell Rep, vol.18, issue.9, pp.2148-2161, 2017.

C. Shih, Y. Chang, and Y. Chen, The PPAR?-SETD8 axis constitutes an epigenetic, p53-independent checkpoint on p21-mediated cellular senescence, Aging Cell, vol.16, issue.4, pp.797-813, 2017.

Y. Qin, H. Ouyang, J. Liu, and Y. Xie, Proteome identification of proteins interacting with histone methyltransferase SET8, Acta Biochim. Biophys. Sin, vol.45, issue.4, pp.303-308, 2013.

R. Huang, Y. Yu, and X. Zong, Monomethyltransferase SETD8 regulates breast cancer metabolism via stabilizing hypoxia-inducible factor 1?, Cancer Lett, vol.390, pp.1-10, 2017.

L. Hou, Q. Li, Y. Yu, M. Li, and D. Zhang, SET8 induces epithelial mesenchymal transition and enhances prostate cancer cell metastasis by cooperating with ZEB1, Mol. Med. Rep, 2015.

!. #&amp;^!,

F. Yang, L. Sun, and Q. Li, SET8 promotes epithelial-mesenchymal transition and confers TWIST dual transcriptional activities, EMBO J, vol.31, issue.1, pp.110-123, 2012.

C. Milite, A. Feoli, and M. Viviano, The emerging role of lysine methyltransferase SETD8 in human diseases, Clin. Epigenetics, vol.8, issue.1, 2016.

A. Ma, W. Yu, and F. Li, Discovery of a Selective, Substrate-Competitive Inhibitor of the Lysine Methyltransferase SETD8, J. Med. Chem, vol.57, issue.15, pp.6822-6833, 2014.

A. Ma, W. Yu, and Y. Xiong, Structure-activity relationship studies of SETD8 inhibitors, Med Chem Commun, vol.5, issue.12, pp.1892-1898, 2014.

G. Blum, G. Ibáñez, and X. Rao, Small-Molecule Inhibitors of SETD8 with Cellular Activity, ACS Chem. Biol, vol.9, issue.11, pp.2471-2478, 2014.

L. Gan, Y. Yang, and Q. Li, Epigenetic regulation of cancer progression by EZH2: from biological insights to therapeutic potential, Biomark. Res, vol.6, issue.1, 2018.

B. Schuettengruber, H. Bourbon, D. Croce, L. Cavalli, and G. , Genome Regulation by Polycomb and Trithorax: 70 Years and Counting, Cell, vol.171, issue.1, pp.34-57, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01596016

E. Conway, E. Healy, and A. P. Bracken, PRC2 mediated H3K27 methylations in cellular identity and cancer, Curr. Opin. Cell Biol, vol.37, pp.42-48, 2015.

S. Aranda, G. Mas, D. Croce, and L. , Regulation of gene transcription by Polycomb proteins, Sci. Adv, vol.1, issue.11, pp.1500737-1500737, 2015.

C. A. Ishak, A. E. Marshall, and D. T. Passos, An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences, Mol. Cell, vol.64, issue.6, pp.1074-1087, 2016.

M. Wassef and R. Margueron, The Multiple Facets of PRC2 Alterations in Cancers, J. Mol. Biol, vol.429, issue.13, pp.1978-1993, 2017.

M. Pan, M. Hsu, L. Chen, and W. Hung, Orchestration of H3K27 methylation: mechanisms and therapeutic implication, Cell. Mol. Life Sci, 2017.

K. J. Ferrari, A. Scelfo, and S. Jammula, Polycomb-Dependent H3K27me1 and H3K27me2 Regulate Active Transcription and Enhancer Fidelity, Mol. Cell, vol.53, issue.1, pp.49-62, 2014.

M. Entrevan, B. Schuettengruber, and G. Cavalli, Regulation of Genome Architecture and Function by Polycomb Proteins, Trends Cell Biol, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01351264

K. P. Eagen, E. L. Aiden, and R. D. Kornberg, Polycomb-mediated chromatin loops revealed by a subkilobase-resolution chromatin interaction map, Proc. Natl. Acad. Sci, vol.114, issue.33, pp.8764-8769, 2017.

C. Lanzuolo, L. Sardo, F. Diamantini, A. Orlando, and V. , PcG Complexes Set the Stage for Epigenetic Inheritance of Gene Silencing in Early S Phase before Replication, PLoS Genet, vol.7, issue.11, 2011.

C. Lanzuolo, L. Sardo, F. Orlando, and V. , Concerted epigenetic signatures inheritance at PcG targets through replication, Cell Cycle, vol.11, issue.7, pp.1296-1300, 2012.

H. Li, R. Liefke, and J. Jiang, Polycomb-like proteins link the PRC2 complex to CpG islands, Nature, vol.549, issue.7671, pp.287-291, 2017.

M. Ku, R. P. Koche, and E. Rheinbay, Genomewide Analysis of PRC1 and PRC2 Occupancy Identifies Two Classes of Bivalent Domains, PLoS Genet, vol.4, issue.10, p.1000242, 2008.

J. W. Højfeldt, A. Laugesen, and B. M. Willumsen, Accurate H3K27 methylation can be established de novo by SUZ12-directed PRC2, Nat. Struct. Mol. Biol, vol.25, issue.3, pp.225-232, 2018.

N. P. Blackledge, A. M. Farcas, and T. Kondo, Variant PRC1 Complex-Dependent H2A Ubiquitylation Drives PRC2 Recruitment and Polycomb Domain Formation, Cell, vol.157, issue.6, pp.1445-1459, 2014.

S. Cooper, M. Dienstbier, and R. Hassan, Targeting Polycomb to Pericentric Heterochromatin in Embryonic Stem Cells Reveals a Role for H2AK119u1 in PRC2 Recruitment, Cell Rep, vol.7, issue.5, pp.1456-1470, 2014.

X. Wang, R. D. Paucek, and A. R. Gooding, Molecular analysis of PRC2 recruitment to DNA in chromatin and its inhibition by RNA, Nat. Struct. Mol. Biol, vol.24, issue.12, pp.1028-1038, 2017.

S. Kaneko, J. Son, S. S. Shen, and D. Reinberg, PRC2 binds to active promoters and contacts nascent RNAs in embryonic stem cells, vol.19, 2014.

A. He, X. Shen, and Q. Ma, PRC2 directly methylates GATA4 and represses its transcriptional activity, Genes Dev, vol.26, issue.1, pp.37-42, 2012.

Y. Sbirkov, C. Kwok, and A. Bhamra, Semi-Quantitative Mass Spectrometry in AML Cells Identifies New Non-Genomic Targets of the EZH2 Methyltransferase, Int. J. Mol. Sci, vol.18, issue.7, p.1440, 2017.

!. #&amp;&lt;!,

J. M. Lee, J. S. Lee, and H. Kim, EZH2 Generates a Methyl Degron that Is Recognized by the DCAF1/DDB1/CUL4 E3 Ubiquitin Ligase Complex, Mol. Cell, vol.48, issue.4, pp.572-586, 2012.

J. Yan, S. Ng, and J. Tay, EZH2 overexpression in natural killer/T-cell lymphoma confers growth advantage independently of histone methyltransferase activity, Blood, vol.121, issue.22, pp.4512-4520, 2013.

H. Xu, K. Xu, and H. H. He, Integrative Analysis Reveals the Transcriptional Collaboration between EZH2 and E2F1 in the Regulation of Cancer-Related Gene Expression, Mol. Cancer Res, vol.14, issue.2, pp.163-172, 2016.

A. R. Öze?, N. Pulliam, and M. G. Ertosun, Protein kinase A-mediated phosphorylation regulates STAT3 activation and oncogenic EZH2 activity, Oncogene, 2018.

E. Kim, M. Kim, and D. Woo, Phosphorylation of EZH2 Activates STAT3 Signaling via STAT3 Methylation and Promotes Tumorigenicity of Glioblastoma Stem-like Cells, Cancer Cell, vol.23, issue.6, pp.839-852, 2013.

S. Lee, Y. Roh, and S. Kim, Activation of EZH2 and SUZ12 Regulated by E2F1 Predicts the Disease Progression and Aggressive Characteristics of Bladder Cancer, Clin. Cancer Res, vol.21, issue.23, pp.5391-5403, 2015.

J. Xiao, MiR-32 Functions as a Tumor Suppressor and Directly Targets EZH2 in Human Oral Squamous Cell Carcinoma, Med. Sci. Monit, vol.20, pp.2527-2535, 2014.

H. Lu, G. Li, and C. Zhou, Regulation and role of post-translational modifications of enhancer of zeste homologue 2 in cancer development, Am. J. Cancer Res, vol.6, issue.12, p.2737, 2016.

L. Aloia, D. Stefano, B. , D. Croce, and L. , Polycomb complexes in stem cells and embryonic development, Development, vol.140, issue.12, pp.2525-2534, 2013.

A. P. Bracken, Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitions, Genes Dev, vol.20, issue.9, pp.1123-1136, 2006.

A. Collinson, A. J. Collier, and N. P. Morgan, Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells, Cell Rep, vol.17, issue.10, pp.2700-2714, 2016.

A. Martinez and G. Cavalli, The role of polycomb group proteins in cell cycle regulation during development, Cell Cycle, vol.5, issue.11, pp.1189-1197, 2006.
URL : https://hal.archives-ouvertes.fr/hal-00082324

A. Piunti, A. Rossi, and A. Cerutti, Polycomb proteins control proliferation and transformation independently of cell cycle checkpoints by regulating DNA replication, Nat. Commun, vol.5, 2014.

F. Picard, J. Cadoret, and B. Audit, The Spatiotemporal Program of DNA Replication Is Associated with Specific Combinations of Chromatin Marks in Human Cells, PLoS Genet, vol.10, issue.5, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00995097

R. Margueron, G. Li, and K. Sarma, Ezh1 and Ezh2 Maintain Repressive Chromatin through Different Mechanisms, Mol. Cell, vol.32, issue.4, pp.503-518, 2008.

L. Abdalkader, T. Oka, and K. Takata, Aberrant differential expression of EZH1 and EZH2 in Polycomb repressive complex 2 among B-and T/NK-cell neoplasms, Pathology (Phila.), 2016.

M. Mochizuki-kashio, K. Aoyama, and G. Sashida, Ezh2 loss in hematopoietic stem cells predisposes mice to develop heterogeneous malignancies in an Ezh1-dependent manner, Blood, vol.126, issue.10, pp.1172-1183, 2015.

J. Xu, Z. Shao, and D. Li, Developmental Control of Polycomb Subunit Composition by GATA Factors Mediates a Switch to Non-Canonical Functions, Mol. Cell, vol.57, issue.2, pp.304-316, 2015.

K. Mozhui and A. K. Pandey, Conserved effect of aging on DNA methylation and association with EZH2 polycomb protein in mice and humans, Mech. Ageing Dev, 2017.

B. Jie, C. Weilong, and C. Ming, Enhancer of zeste homolog 2 depletion induces cellular senescence via histone demethylation along the INK4/ARF locus, Int. J. Biochem. Cell Biol, vol.65, pp.104-112, 2015.

I. Hidalgo, A. Herrera-merchan, and J. M. Ligos, Ezh1 Is Required for Hematopoietic Stem Cell Maintenance and Prevents Senescence-like Cell Cycle Arrest, Cell Stem Cell, vol.11, issue.5, pp.649-662, 2012.

A. P. Bracken, D. Kleine-kohlbrecher, and N. Dietrich, The Polycomb group proteins bind throughout the INK4A-ARF locus and are disassociated in senescent cells, Genes Dev, vol.21, issue.5, pp.525-530, 2007.

K. Kia, S. , S. Kartalaei, P. Farahbakhshian, and E. , EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence, Epigenetics Chromatin, vol.2, p.16, 2009.

A. Iannetti, A. C. Ledoux, and S. J. Tudhope, Regulation of p53 and Rb Links the Alternative NF-?B Pathway to EZH2 Expression and Cell Senescence, PLoS Genet, vol.10, issue.9, p.1004642, 2014.

H. Agherbi, A. Gaussmann-wenger, and C. Verthuy, Polycomb Mediated Epigenetic Silencing and Replication Timing at the INK4a/ARF Locus during Senescence, PLoS ONE, vol.4, issue.5, 2009.
URL : https://hal.archives-ouvertes.fr/hal-00408485

J. Savickien?, S. Baronait?, A. Zentelyt?, G. Treigyt?, and R. Navakauskien?, Senescence-Associated Molecular and Epigenetic Alterations in Mesenchymal Stem Cell Cultures from Amniotic Fluid of Normal and Fetus-Affected Pregnancy, Stem Cells Int, 2016.

A. Tzatsos, P. Paskaleva, and S. Lymperi, Lysine-specific Demethylase 2B (KDM2B)-let-7-Enhancer of Zester Homolog 2 (EZH2) Pathway Regulates Cell Cycle Progression and Senescence in Primary Cells, J. Biol. Chem, vol.286, issue.38, pp.33061-33069, 2011.

T. Ito, Y. V. Teo, S. A. Evans, N. Neretti, and J. M. Sedivy, Regulation of Cellular Senescence by Polycomb Chromatin Modifiers through Distinct DNA Damage-and Histone Methylation-Dependent Pathways, Cell Rep, vol.22, issue.13, pp.3480-3492, 2018.

Y. Wen, J. Cai, Y. Hou, Z. Huang, and Z. Wang, Role of EZH2 in cancer stem cells: from biological insight to a therapeutic target, Oncotarget, vol.8, issue.23, 2017.

A. Iwama, Polycomb repressive complexes in hematological malignancies, Blood, p.2017, 2017.

L. Herviou, G. Cavalli, G. Cartron, B. Klein, and J. Moreaux, EZH2 in normal hematopoiesis and hematological malignancies, Oncotarget, vol.7, issue.3, p.2284, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01275235

R. Ryan, M. Nitta, and D. Borger, EZH2 Codon 641 Mutations are Common in BCL2-Rearranged Germinal Center B Cell Lymphomas, PLoS ONE, vol.6, issue.12, p.28585, 2011.

H. M. Ott, A. P. Graves, and M. B. Pappalardi, A687V EZH2 Is a Driver of Histone H3 Lysine 27 (H3K27) Hypertrimethylation, Mol. Cancer Ther, vol.13, issue.12, pp.3062-3073, 2014.

R. D. Morin, N. A. Johnson, and T. M. Severson, Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin, Nat. Genet, vol.42, issue.2, pp.181-185, 2010.

M. T. Mccabe, A. P. Graves, and G. Ganji, Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27), Proc. Natl. Acad. Sci, vol.109, issue.8, pp.2989-2994, 2012.

M. Shirahata-adachi, C. Iriyama, and A. Tomita, Altered EZH2 splicing and expression is associated with impaired histone H3 lysine 27 tri-Methylation in myelodysplastic syndrome, Leuk. Res, vol.63, pp.90-97, 2017.

S. Göllner, T. Oellerich, and S. Agrawal-singh, Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia, Nat. Med, 2016.

K. Yan, C. Lin, and T. Liao, EZH2 in Cancer Progression and Potential Application in Cancer Therapy: A Friend or Foe?, Int. J. Mol. Sci, vol.18, issue.6, p.1172, 2017.

X. Song, L. Zhang, and T. Gao, Selective inhibition of EZH2 by ZLD10A blocks H3K27 methylation and kills mutant lymphoma cells proliferation, Biomed. Pharmacother, vol.81, pp.288-294, 2016.

W. Qi, H. Chan, and L. Teng, Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation, Proc. Natl. Acad. Sci, vol.109, issue.52, pp.21360-21365, 2012.

N. Gulati, W. Béguelin, and L. Giulino-roth, Enhancer of zeste homolog 2 (EZH2) inhibitors, Leuk. Lymphoma, pp.1-12, 2018.

K. W. Kuntz, J. E. Campbell, and H. Keilhack, The Importance of Being Me: Magic Methyls, Methyltransferase Inhibitors, and the Discovery of Tazemetostat, J. Med. Chem, vol.59, issue.4, pp.1556-1564, 2016.

J. E. Campbell, K. W. Kuntz, and S. K. Knutson, Orally-Available EZH2 Inhibitor with Robust in Vivo Activity, ACS Med. Chem. Lett, vol.6, issue.5, pp.491-495, 2015.

G. S. Van-aller, M. B. Pappalardi, and H. M. Ott, Long Residence Time Inhibition of EZH2 in Activated Polycomb Repressive Complex 2, ACS Chem. Biol, vol.9, issue.3, pp.622-629, 2014.

R. T. Kurmasheva, M. Sammons, and E. Favours, Initial testing (stage 1) of tazemetostat (EPZ-6438), a novel EZH2 inhibitor, by the Pediatric Preclinical Testing Program: Kurmasheva et al. Pediatr, Blood Cancer, 2016.

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Y. Huang, J. Zhang, and Z. Yu, Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy, J. Med. Chem, vol.60, issue.6, pp.2215-2226, 2017.

, Rare Tumors in Kids May Respond to Tazemetostat, Cancer Discov, vol.8, issue.1, p.5, 2018.

M. Wiese, F. Schill, and D. Sturm, No Significant Cytotoxic Effect of the EZH2 Inhibitor Tazemetostat (EPZ-6438) on Pediatric Glioma Cells with Wildtype Histone 3 or Mutated Histone 3.3, Klin. Pädiatr, vol.228, issue.03, pp.113-117, 2016.

A. Italiano, J. Soria, and M. Toulmonde, an EZH2 inhibitor, in relapsed or refractory B-cell non-Hodgkin lymphoma and advanced solid tumours: a first-in-human, open-label, phase 1 study, Lancet Oncol, 2018.

V. Gibaja, F. Shen, and J. Harari, Development of secondary mutations in wild-type and mutant EZH2 alleles cooperates to confer resistance to EZH2 inhibitors, Oncogene, vol.35, issue.5, pp.558-566, 2016.

S. Garapaty-rao, C. Nasveschuk, and A. Gagnon, Identification of EZH2 and EZH1 Small Molecule Inhibitors with Selective Impact on Diffuse Large B Cell Lymphoma Cell Growth, Chem. Biol, vol.20, issue.11, pp.1329-1339, 2013.

D. Honma, O. Kanno, and J. Watanabe, Novel orally bioavailable EZH1/2 dual inhibitors with greater antitumor efficacy than an EZH2 selective inhibitor, Cancer Sci, 2017.

K. D. Konze, A. Ma, and F. Li, An Orally Bioavailable Chemical Probe of the Lysine Methyltransferases EZH2 and EZH1, ACS Chem. Biol, vol.8, issue.6, pp.1324-1334, 2013.

Y. Yu and K. Lin, Factors That Regulate the Generation of Antibody-Secreting Plasma Cells, Adv. Immunol, vol.131, pp.61-99, 2016.

S. P. Methot, D. Noia, and J. M. , Molecular Mechanisms of Somatic Hypermutation and Class Switch Recombination, Adv. Immunol, vol.133, pp.37-87, 2017.

J. L. Halliley, C. M. Tipton, and J. Liesveld, Long-Lived Plasma Cells Are Contained within the CD19?CD38hiCD138+ Subset in Human Bone Marrow, Immunity, vol.43, issue.1, pp.132-145, 2015.

E. Hammarlund, A. Thomas, and I. J. Amanna, Plasma cell survival in the absence of B cell memory, Nat. Commun, vol.8, 2017.

M. J. Mccarron, P. W. Park, and D. R. Fooksman, CD138 mediates selection of mature plasma cells by regulating their survival, Blood, vol.129, issue.20, pp.2749-2759, 2017.

V. Biajoux, J. Natt, and C. Freitas, Efficient Plasma Cell Differentiation and Trafficking Require Cxcr4 Desensitization, Cell Rep, vol.17, issue.1, pp.193-205, 2016.
URL : https://hal.archives-ouvertes.fr/inserm-01401695

K. Nera, M. K. Kyläniemi, and O. Lassila, Regulation of B Cell to Plasma Cell Transition within the Follicular B Cell Response, Scand. J. Immunol, vol.82, issue.3, pp.225-234, 2015.

M. Jourdan, M. Cren, and N. Robert, IL-6 supports the generation of human long-lived plasma cells in combination with either APRIL or stromal cell-soluble factors, Leukemia, vol.28, issue.8, pp.1647-1656, 2014.
URL : https://hal.archives-ouvertes.fr/hal-00974531

S. L. Nutt, P. D. Hodgkin, D. M. Tarlinton, and L. M. Corcoran, The generation of antibody-secreting plasma cells, Nat. Rev. Immunol, vol.15, issue.3, pp.160-171, 2015.

M. Aronov and B. Tirosh, Metabolic Control of Plasma Cell Differentiation-What We Know and What We Don't Know, J. Clin. Immunol, vol.36, issue.S1, pp.12-17, 2016.

H. W. Auner, C. Beham-schmid, N. Dillon, and P. Sabbattini, The life span of short-lived plasma cells is partly determined by a block on activation of apoptotic caspases acting in combination with endoplasmic reticulum stress, Blood, vol.116, issue.18, pp.3445-3455, 2010.

N. Pelletier, M. Casamayor-palleja, D. Luca, and K. , The Endoplasmic Reticulum Is a Key Component of the Plasma Cell Death Pathway, J. Immunol, vol.176, issue.3, pp.1340-1347, 2006.

D. D. Jones, B. T. Gaudette, and J. R. Wilmore, mTOR has distinct functions in generating versus sustaining humoral immunity, J. Clin. Invest, vol.126, issue.11, pp.4250-4261

T. Inoue, I. Moran, R. Shinnakasu, T. G. Phan, and T. Kurosaki, Generation of memory B cells and their reactivation, Immunol. Rev, vol.283, issue.1, pp.138-149, 2018.

K. A. Pape and M. K. Jenkins, Do Memory B Cells Form Secondary Germinal Centers?: It Depends, Cold Spring Harb. Perspect. Biol, 2017.

M. Jourdan, A. Caraux, and G. Caron, Characterization of a Transitional Preplasmablast Population in the Process of Human B Cell to Plasma Cell Differentiation, J. Immunol, vol.187, issue.8, pp.3931-3941, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00743965

!. #^e!,

A. L. Shaffer, K. Lin, and T. C. Kuo, Blimp-1 Orchestrates Plasma Cell Differentiation by Extinguishing the Mature B Cell Gene Expression Program, Immunity, vol.17, issue.1, pp.51-62, 2002.

L. M. Corcoran and D. M. Tarlinton, Regulation of germinal center responses, memory B cells and plasma cell formation-an update, Curr. Opin. Immunol, vol.39, pp.59-67, 2016.

J. Alinikula, K. Nera, S. Junttila, and O. Lassila, Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation, Eur. J. Immunol, vol.41, issue.8, pp.2404-2413, 2011.

K. Igarashi, K. Ochiai, A. Itoh-nakadai, and A. Muto, Orchestration of plasma cell differentiation by Bach2 and its gene regulatory network, Immunol. Rev, vol.261, issue.1, pp.116-125, 2014.

S. Chen, M. Miyazaki, K. Fisch, A. N. Chang, and C. Murre, Id3 Orchestrates Germinal Center B Cell Development. Mol. Cell. Biol, pp.150-166, 2016.

S. N. Willis, J. Tellier, and Y. Liao, Environmental sensing by mature B cells is controlled by the transcription factors PU.1 and SpiB, Nat. Commun, vol.8, 2017.

M. Minnich, H. Tagoh, and P. Bönelt, Multifunctional role of the transcription factor Blimp-1 in coordinating plasma cell differentiation, Nat. Immunol, vol.17, issue.3, pp.331-343, 2016.

M. Shapiro-shelef and K. Calame, Plasma cell differentiation and multiple myeloma, Curr. Opin. Immunol, vol.16, issue.2, pp.226-234, 2004.

C. Zhu, G. Chen, Y. Zhao, X. Gao, and J. Wang, Regulation of the Development and Function of B Cells by ZBTB Transcription Factors, Front. Immunol, vol.9, 2018.

D. Piovesan, J. Tempany, D. Pietro, and A. , c-Myb Regulates the T-Bet-Dependent Differentiation Program in B Cells to Coordinate Antibody Responses, Cell Rep, vol.19, issue.3, pp.461-470, 2017.

D. A. Francis, J. G. Karras, X. Ke, R. Sen, and T. L. Rothstein, Induction of the transcription factors NF-KB, AP-1 and NF-AT during B cell stimulation through the CD40 receptor, p.11, 2014.

S. Gerondakis and U. Siebenlist, Roles of the NF-B Pathway in Lymphocyte Development and Function, Cold Spring Harb. Perspect. Biol, vol.2, issue.5, pp.182-000182, 2010.

N. Heise, D. Silva, N. S. Silva, and K. , Germinal center B cell maintenance and differentiation are controlled by distinct NF-?B transcription factor subunits, J. Exp. Med, vol.211, issue.10, pp.2103-2118, 2014.

D. Mielenz, B. Grötsch, and J. David, Repressing the repressor: Fra1 controls plasma cell generation, Oncotarget, vol.6, issue.20, p.17861, 2015.

B. Grötsch, S. Brachs, and C. Lang, The AP-1 transcription factor Fra1 inhibits follicular B cell differentiation into plasma cells, J. Exp. Med, vol.211, issue.11, pp.2199-2212, 2014.

D. A. Lebman and J. S. Edmiston, The role of TGF-? in growth, differentiation, and maturation of B lymphocytes, Microbes Infect, vol.1, issue.15, pp.1297-1304, 1999.

D. Khiem, J. G. Cyster, J. J. Schwarz, and B. L. Black, A p38 MAPK-MEF2C pathway regulates B-cell proliferation, Proc. Natl. Acad. Sci, vol.105, issue.44, pp.17067-17072, 2008.

S. De, B. Zhang, and T. Shih, B Cell-Intrinsic Role for IRF5 in TLR9/BCR-Induced Human B Cell Activation, Proliferation, and Plasmablast Differentiation, Front. Immunol, vol.8, 2018.

M. Ushijima, T. Uruno, and A. Nishikimi, The Rac Activator DOCK2 Mediates Plasma Cell Differentiation and IgG Antibody Production, Front. Immunol, vol.9, 2018.

E. Kleiman, H. Jia, S. Loguercio, A. I. Su, and A. J. Feeney, YY1 plays an essential role at all stages of B-cell differentiation, Proc. Natl. Acad. Sci, vol.113, issue.27, pp.3911-3920, 2016.

W. Shi, Y. Liao, and S. N. Willis, Transcriptional profiling of mouse B cell terminal differentiation defines a signature for antibody-secreting plasma cells, Nat. Immunol, vol.16, issue.6, pp.663-673, 2015.

M. Jourdan, A. Caraux, D. Vos, and J. , An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization, Blood, vol.114, issue.25, pp.5173-5181, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00446133

X. Fang, Y. Tong, and H. Tian, Rapid de novo generation of antigen specific human B cells with expression of Blimp!1 and AID by in vitro immunization, Exp. Cell Res, vol.352, issue.1, pp.53-62, 2017.

K. L. Hung, I. Meitlis, and M. Hale, Engineering Protein-Secreting Plasma Cells by Homology-Directed Repair in Primary Human B Cells, Mol. Ther, vol.26, issue.2, pp.456-467, 2018.

L. Gallou, S. Caron, G. Delaloy, and C. , IL-2 Requirement for Human Plasma Cell Generation: Coupling Differentiation and Proliferation by Enhancing MAPK-ERK Signaling, J. Immunol, vol.189, issue.1, pp.161-173, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00869090

J. Huggins, T. Pellegrin, and R. E. Felgar, CpG DNA activation and plasma-cell differentiation of CD27-naive human B cells, Blood, vol.109, issue.4, pp.1611-1619, 2007.

!. #^,

S. G. Tangye, D. T. Avery, and P. D. Hodgkin, A Division-Linked Mechanism for the Rapid Generation of Ig-Secreting Cells from Human Memory B Cells, J. Immunol, vol.170, issue.1, pp.261-269, 2003.

A. Kassambara, T. Rème, and M. Jourdan, An Easy-to-Use Web Tool for Gene Expression Data Analysis. Application to Investigate the Molecular Events in the Differentiation of B Cells into Plasma Cells, PLOS Comput. Biol, vol.11, issue.1, p.1004077, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01112225

J. Meinzinger, H. Jäck, and K. Pracht, miRNA meets plasma cells "How tiny RNAs control antibody responses, Clin. Immunol, vol.186, pp.3-8, 2018.

C. A. White, E. J. Pone, and T. Lam, Histone Deacetylase Inhibitors Upregulate B Cell microRNAs That Silence AID and Blimp-1 Expression for Epigenetic Modulation of Antibody and Autoantibody Responses, J. Immunol, vol.193, issue.12, pp.5933-5950, 2014.

M. Gururajan, C. L. Haga, and S. Das, MicroRNA 125b inhibition of B cell differentiation in germinal centers, Int. Immunol, vol.22, issue.7, pp.583-592, 2010.

T. Shen, H. N. Sanchez, H. Zan, and P. Casali, Genome-Wide Analysis Reveals Selective Modulation of microRNAs and mRNAs by Histone Deacetylase Inhibitor in B Cells Induced to Undergo Class-Switch DNA Recombination and Plasma Cell Differentiation, Front. Immunol, vol.6, 2015.

N. Bartolomé-izquierdo, V. G. De-yébenes, and A. F. Álvarez-prado, miR-28 regulates the germinal center reaction and blocks tumor growth in preclinical models of non-Hodgkin lymphoma, Blood, vol.129, issue.17, pp.2408-2419, 2017.

H. N. Au--sanchez, T. Au--shen, and D. Au--garcia, Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Classswitch DNA Recombination and Plasma Cell Differentiation, J. Vis. Exp, issue.127, p.55135, 2017.

M. Porstner, R. Winkelmann, and P. Daum, miR-148a promotes plasma cell differentiation and targets the germinal center transcription factors Mitf and Bach2: Molecular immunology, Eur. J. Immunol, vol.45, issue.4, pp.1206-1215, 2015.

A. Kassambara, M. Jourdan, and A. Bruyer, Global miRNA expression analysis identifies novel key regulators of plasma cell differentiation and malignant plasma cell, Nucleic Acids Res, vol.45, issue.10, pp.5639-5652, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01533425

R. P. Schuyler, A. Merkel, and E. Raineri, Distinct Trends of DNA Methylation Patterning in the Innate and Adaptive Immune Systems, Cell Rep, vol.17, issue.8, pp.2101-2111, 2016.

M. Kulis, A. Merkel, and S. Heath, Whole-genome fingerprint of the DNA methylome during human B-cell differentiation, Nat. Genet, vol.47, issue.7, pp.746-756, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01163753

R. Shaknovich, L. Cerchietti, and L. Tsikitas, DNA methyltransferase 1 and DNA methylation patterning contribute to germinal center B-cell differentiation, Blood, vol.118, issue.13, pp.3559-3569, 2011.

A. Y. Lai, D. Mav, and R. Shah, DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation, Genome Res, vol.23, issue.12, pp.2030-2041, 2013.

P. M. Dominguez, M. Teater, and N. Chambwe, DNA Methylation Dynamics of Germinal Center B Cells Are Mediated by AID. Cell Rep, vol.12, issue.12, pp.2086-2098, 2015.

A. R. Ramiro and V. M. Barreto, Activation-induced cytidine deaminase and active cytidine demethylation, Trends Biochem. Sci, vol.40, issue.3, pp.172-181, 2015.

E. L. Fritz, B. R. Rosenberg, and K. Lay, A comprehensive analysis of the effects of the deaminase AID on the transcriptome and methylome of activated B cells, Nat. Immunol, vol.14, issue.7, pp.749-755, 2013.

C. S. Nabel, H. Jia, and Y. Ye, AID/APOBEC deaminases disfavor modified cytosines implicated in DNA demethylation, Nat. Chem. Biol, vol.8, issue.9, pp.751-758, 2012.

B. G. Barwick, C. D. Scharer, A. Bally, and J. M. Boss, Plasma cell differentiation is coupled to divisiondependent DNA hypomethylation and gene regulation, Nat. Immunol, 2016.

G. Caron, M. Hussein, and M. Kulis, Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells, Cell Rep, vol.13, issue.5, pp.1059-1071, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01219671

J. I. Martin-subero and C. C. Oakes, Charting the dynamic epigenome during B-cell development, Semin. Cancer Biol, 2017.

G. Hannum, J. Guinney, and L. Zhao, Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates, Mol. Cell, vol.49, issue.2, pp.359-367, 2013.

!. #^#!,

H. Heyn, E. Vidal, and H. J. Ferreira, Epigenomic analysis detects aberrant super-enhancer DNA methylation in human cancer, Genome Biol, vol.17, issue.1, 2016.

S. Horvath, DNA methylation age of human tissues and cell types, Genome Biol, vol.14, issue.10, p.115, 2013.

S. C. Zheng, M. Widschwendter, and A. E. Teschendorff, Epigenetic drift, epigenetic clocks and cancer risk, Epigenomics, vol.8, issue.5, pp.705-719, 2016.

D. Lowe, S. Horvath, and K. Raj, Epigenetic clock analyses of cellular senescence and ageing, Oncotarget, vol.7, issue.8, pp.8524-8531, 2016.

K. Declerck, V. Berghe, and W. , Back to the future: Epigenetic clock plasticity towards healthy aging, Mech. Ageing Dev, 2018.

E. N. Gal-yam, G. Egger, and L. Iniguez, Frequent switching of Polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line, Proc. Natl. Acad. Sci, vol.105, issue.35, pp.12979-12984, 2008.

Á. Muñoz-lópez, E. Van-roon, and D. Romero-moya, Cellular Ontogeny and Hierarchy Influence the Reprogramming Efficiency of Human B Cells into Induced Pluripotent Stem Cells: B-Cell Lineage Reprogramming, STEM CELLS, vol.34, issue.3, pp.581-587, 2016.

. Kieffer-kwon-k-r, K. Nimura, and S. Rao, Myc Regulates Chromatin Decompaction and Nuclear Architecture during B Cell Activation, Mol. Cell, vol.67, issue.4, pp.566-578, 2017.

K. L. Bunting, T. D. Soong, and R. Singh, Multi-tiered Reorganization of the Genome during B Cell Affinity Maturation Anchored by a Germinal Center-Specific Locus Control Region, Immunity, vol.45, issue.3, pp.497-512, 2016.

A. Pérez-garcía, E. Marina-zárate, and Á. F. Álvarez-prado, CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation, Nat. Commun, vol.8, 2017.

A. Bortnick, Z. He, and M. Aubrey, An inter-chromosomal transcription hub activates the unfolded protein response in plasma cells, 2018.

C. D. Scharer, B. G. Barwick, M. Guo, A. Bally, and J. M. Boss, Plasma cell differentiation is controlled by multiple cell division-coupled epigenetic programs, Nat. Commun, vol.9, 2018.

J. Baxter, S. Sauer, and A. Peters, Histone hypomethylation is an indicator of epigenetic plasticity in quiescent lymphocytes, EMBO J, vol.23, issue.22, pp.4462-4472, 2004.

D. Wen, L. A. Banaszynski, Z. Rosenwaks, A. Cd, and R. S. H3, 3 replacement facilitates epigenetic reprogramming of donor nuclei in somatic cell nuclear transfer embryos, Nucleus, vol.5, issue.5, pp.369-375, 2014.

O. Weth, C. Paprotka, and K. Gunther, CTCF induces histone variant incorporation, erases the H3K27me3 histone mark and opens chromatin, Nucleic Acids Res, vol.42, pp.11941-11951, 2014.

M. Waibel, A. J. Christiansen, and M. L. Hibbs, Manipulation of B-cell responses with histone deacetylase inhibitors, Nat. Commun, vol.6, issue.1, 2015.

A. Kienzler, M. Rizzi, M. Reith, S. L. Nutt, and H. Eibel, Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid, J. Allergy Clin. Immunol, vol.131, issue.6, pp.1695-1699, 2013.

X. Jiang, Y. Chou, and L. Jones, Epigenetic Regulation of Antibody Responses by the Histone H2A Deubiquitinase MYSM1, Sci. Rep, vol.5, p.13755, 2015.

M. R. Green, H. Yoon, and J. M. Boss, Epigenetic Regulation during B Cell Differentiation Controls CIITA Promoter Accessibility, J. Immunol, vol.177, issue.6, pp.3865-3873, 2006.

G. Li, H. Zan, Z. Xu, and P. Casali, Epigenetics of the antibody response, Trends Immunol, vol.34, issue.9, pp.460-470, 2013.

N. Fujita, D. L. Jaye, and C. Geigerman, MTA3 and the Mi-2/NuRD Complex Regulate Cell Fate during B Lymphocyte Differentiation, Cell, vol.119, issue.1, pp.75-86, 2004.

B. Barneda-zahonero, L. Roman-gonzalez, O. Collazo, T. Mahmoudi, and M. Parra, Epigenetic Regulation of B Lymphocyte Differentiation, Transdifferentiation, and Reprogramming, Comp. Funct. Genomics, vol.2012, 2012.

H. Tanaka, A. Muto, and H. Shima, Epigenetic Regulation of the Blimp-1 Gene (Prdm1) in B Cells Involves Bach2 and Histone Deacetylase 3, J. Biol. Chem, vol.291, issue.12, pp.6316-6330, 2016.

Y. Bao and X. Cao, Epigenetic Control of B Cell Development and B-Cell-Related Immune Disorders, Clin. Rev. Allergy Immunol, vol.50, issue.3, pp.301-311, 2016.

!. #^$!,

S. Su, Y. , H. Chiu, and Y. , Involvement of Histone Demethylase LSD1 in Blimp-1-Mediated Gene Repression during Plasma Cell Differentiation, Mol. Cell. Biol, vol.29, issue.6, pp.1421-1431, 2009.

J. Yu, C. Angelin-duclos, J. Greenwood, J. Liao, and K. Calame, Transcriptional Repression by Blimp-1 (PRDI-BF1) Involves Recruitment of Histone Deacetylase, Mol. Cell. Biol, vol.20, issue.7, pp.2592-2603, 2000.

H. Zan and P. Casali, Epigenetics of Peripheral B-Cell Differentiation and the Antibody Response, Front. Immunol, vol.6, 2015.

Z. Ying, M. Mei, and P. Zhang, Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription, J. Immunol, vol.195, issue.4, pp.1538-1547, 2015.

S. Infantino, A. Light, and K. O&apos;donnell, Arginine methylation catalyzed by PRMT1 is required for B cell activation and differentiation, Nat. Commun, vol.8, 2017.

M. Caganova, C. Carrisi, and G. Varano, Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis, J. Clin. Invest, vol.123, issue.12, pp.5009-5022, 2013.

W. Béguelin, R. Popovic, and M. Teater, EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation, Cancer Cell, vol.23, issue.5, pp.677-692, 2013.

I. Velichutina, R. Shaknovich, and H. Geng, EZH2-mediated epigenetic silencing in germinal center B cells contributes to proliferation and lymphomagenesis, Blood, vol.116, issue.24, pp.5247-5255, 2010.

F. M. Raaphorst, F. J. Van-kemenade, and E. Fieret, Cutting Edge: Polycomb Gene Expression Patterns Reflect Distinct B Cell Differentiation Stages in Human Germinal Centers, J. Immunol, vol.164, issue.1, pp.1-4, 2000.

W. Béguelin, M. A. Rivas, C. Fernández, and M. T. , EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop, Nat. Commun, vol.8, issue.1, 2017.

W. Béguelin, M. Teater, and M. D. Gearhart, EZH2 and BCL6 Cooperate to Assemble CBX8-BCOR Complex to Repress Bivalent Promoters, Mediate Germinal Center Formation and Lymphomagenesis, Cancer Cell, vol.30, issue.2, pp.197-213, 2016.

T. Berg, S. Thoene, and D. Yap, A transgenic mouse model demonstrating the oncogenic role of mutations in the polycomb-group gene EZH2 in lymphomagenesis, Blood, vol.123, issue.25, pp.3914-3924, 2014.

W. H. Neo, J. F. Lim, R. Grumont, S. Gerondakis, and I. Su, c-Rel Regulates Ezh2 Expression in Activated Lymphocytes and Malignant Lymphoid Cells, J. Biol. Chem, vol.289, issue.46, pp.31693-31707, 2014.

M. Guo, M. J. Price, and D. G. Patterson, EZH2 Represses the B Cell Transcriptional Program and Regulates Antibody-Secreting Cell Metabolism and Antibody Production, J. Immunol, vol.200, issue.3, pp.1039-1052, 2018.

E. Braggio, K. M. Kortüm, and A. K. Stewart, SnapShot: Multiple Myeloma, Cancer Cell, vol.28, issue.5, pp.678-678, 2015.

S. K. Kumar and S. V. Rajkumar, The multiple myelomas -current concepts in cytogenetic classification and therapy, Nat. Rev. Clin. Oncol, 2018.

S. K. Kumar, V. Rajkumar, and R. A. Kyle, Multiple myeloma, Nat. Rev. Dis. Primer, vol.3, p.17046, 2017.
URL : https://hal.archives-ouvertes.fr/inserm-01631468

F. Zhan, The molecular classification of multiple myeloma, Blood, vol.108, issue.6, pp.2020-2028, 2006.

J. B. Egan, C. Shi, and W. Tembe, Whole-genome sequencing of multiple myeloma from diagnosis to plasma cell leukemia reveals genomic initiating events, evolution, and clonal tides, Blood, vol.120, issue.5, pp.1060-1066, 2012.

J. J. Keats, M. Chesi, and J. B. Egan, Clonal competition with alternating dominance in multiple myeloma, Blood, vol.120, issue.5, pp.1067-1076, 2012.

N. Bolli, H. Avet-loiseau, and D. C. Wedge, Heterogeneity of genomic evolution and mutational profiles in multiple myeloma, Nat. Commun, vol.5, 2014.

N. J. Bahlis, Keats et al,1 Egan et al,2 and Walker et al3 provide a genomewide snapshot of the clonal landscape in multiple myeloma (MM) illustrating the complexity of the evolutionary process and the dynamics of clonal evolution over time, this issue of Blood

G. J. Morgan, B. A. Walker, and F. E. Davies, The genetic architecture of multiple myeloma, Nat. Rev. Cancer, vol.12, issue.5, pp.335-348, 2012.

T. Paíno and B. Paiva, Phenotypic ! #^%! identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential, Grupo Español de MM), vol.29, issue.5, pp.1186-1194, 2015.

B. Paiva, N. Puig, and M. Cedena, Differentiation stage of myeloma plasma cells: biological and clinical significance, Leukemia, 2016.

F. Magrangeas, H. Avet-loiseau, and W. Gouraud, Minor clone provides a reservoir for relapse in multiple myeloma, Leukemia, vol.27, issue.2, pp.473-481, 2013.

A. Chaidos, C. P. Barnes, and G. Cowan, Clinical drug resistance linked to interconvertible phenotypic and functional states of tumor-propagating cells in multiple myeloma, Blood, vol.121, issue.2, pp.318-328, 2013.

B. A. Walker, C. P. Wardell, and L. Chiecchio, Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma, Blood, vol.117, issue.2, pp.553-562, 2011.

C. J. Heuck, J. Mehta, and T. Bhagat, Myeloma Is Characterized by Stage-Specific Alterations in DNA Methylation That Occur Early during Myelomagenesis, J. Immunol, vol.190, issue.6, pp.2966-2975, 2013.

V. Bollati, S. Fabris, and V. Pegoraro, Differential repetitive DNA methylation in multiple myeloma molecular subgroups, Carcinogenesis, vol.30, issue.8, pp.1330-1335, 2009.

J. I. Sive, A. Feber, and D. Smith, Global hypomethylation in myeloma is associated with poor prognosis, Br. J. Haematol, vol.172, issue.3, pp.473-475, 2016.

X. Agirre, G. Castellano, and M. Pascual, Whole-epigenome analysis in multiple myeloma reveals DNA hypermethylation of B cell-specific enhancers, Clin. Lymphoma Myeloma Leuk, vol.15, pp.86-87, 2015.

N. Amodio, D. &apos;aquila, P. Passarino, G. Tassone, P. Bellizzi et al., Epigenetic modifications in multiple myeloma: recent advances on the role of DNA and histone methylation, Expert Opin. Ther. Targets, vol.21, issue.1, pp.91-101, 2017.

J. G. Turner, J. L. Gump, and C. Zhang, ABCG2 expression, function, and promoter methylation in human multiple myeloma, Blood, vol.108, issue.12, pp.3881-3889, 2006.

C. Chim, R. Liang, M. Leung, and Y. Kwong, Aberrant gene methylation implicated in the progression of monoclonal gammopathy of undetermined significance to multiple myeloma, J. Clin. Pathol, vol.60, issue.1, pp.104-106, 2007.

O. Galm, S. Wilop, and J. Reichelt, DNA methylation changes in multiple myeloma, Leukemia, vol.18, issue.10, pp.1687-1692, 2004.

G. Heller, W. M. Schmidt, and B. Ziegler, Genome-Wide Transcriptional Response to 5-Aza-2'-Deoxycytidine and Trichostatin A in Multiple Myeloma Cells, Cancer Res, vol.68, issue.1, pp.44-54, 2008.

E. Braggio, A. Maiolino, and M. E. Gouveia, Methylation status of nine tumor suppressor genes in multiple myeloma, Int. J. Hematol, vol.91, issue.1, pp.87-96, 2010.

M. F. Kaiser, D. C. Johnson, and P. Wu, Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma, Blood, vol.122, issue.2, pp.219-226, 2013.

Y. Zhou, L. Chen, and B. Barlogie, High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2, Proc. Natl. Acad. Sci. U. S. A, vol.107, issue.17, pp.7904-7909, 2010.

C. Pawlyn, M. F. Kaiser, and C. Heuck, The spectrum and clinical impact of epigenetic modifier mutations in myeloma, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.22, issue.23, pp.5783-5794, 2016.

N. Rastgoo, J. Abdi, J. Hou, and H. Chang, Role of epigenetics-microRNA axis in drug resistance of multiple myeloma, J. Hematol. Oncol.J Hematol Oncol, vol.10, issue.1, 2017.

Y. Yang, J. Lin, and Z. Ma, Potential roles of microRNAs and their target genes in human multiple myeloma, Eur. J. Haematol, vol.99, issue.2, pp.178-185, 2017.

H. Gao, H. Wang, and W. Yang, Identification of key genes and construction of microRNA-mRNA regulatory networks in multiple myeloma by integrated multiple GEO datasets using bioinformatics analysis, Int. J. Hematol, 2017.

E. Morelli, E. Leone, and M. Cantafio, Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo, Leukemia, vol.29, issue.11, pp.2173-2183, 2015.

E. Leone, E. Morelli, D. Martino, and M. T. , Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.19, issue.8, pp.2096-2106, 2013.

!. #^&amp;!,

Y. Zhou, L. Chen, and B. Barlogie, High-risk myeloma is associated with global elevation of miRNAs and overexpression of EIF2C2/AGO2, Proc. Natl. Acad. Sci. U. S. A, vol.107, issue.17, pp.7904-7909, 2010.

D. Martino, M. T. Gullà, A. Cantafio, and M. , In Vitro and in Vivo Anti-tumor Activity of miR-221/222 Inhibitors in Multiple Myeloma, Oncotarget, vol.4, issue.2, pp.242-255, 2013.

N. C. Gutiérrez, M. E. Sarasquete, and I. Misiewicz-krzeminska, Deregulation of microRNA expression in the different genetic subtypes of multiple myeloma and correlation with gene expression profiling, Leukemia, vol.24, issue.3, pp.629-637, 2010.

N. Amodio, M. A. Stamato, and A. M. Gullà, Therapeutic Targeting of miR-29b/HDAC4 Epigenetic Loop in Multiple Myeloma, Mol. Cancer Ther, vol.15, issue.6, pp.1364-1375, 2016.

M. Y. Murray, S. A. Rushworth, L. Zaitseva, K. M. Bowles, and D. J. Macewan, Attenuation of dexamethasoneinduced cell death in multiple myeloma is mediated by miR-125b expression, Cell Cycle, vol.12, issue.13, pp.2144-2153, 2013.

T. Yamamoto, N. Kosaka, Y. Hattori, and T. Ochiya, A Challenge to Aging Society by microRNA in Extracellular Vesicles: microRNA in Extracellular Vesicles as Promising Biomarkers and Novel Therapeutic Targets in Multiple Myeloma, J. Clin. Med, vol.7, issue.3, p.55, 2018.

C. Sathitruangsak, C. H. Righolt, and L. Klewes, Distinct and shared three!dimensional chromosome organization patterns in lymphocytes, monoclonal gammopathy of undetermined significance and multiple myeloma, Int. J. Cancer, vol.140, issue.2, pp.400-410, 2017.

C. Sathitruangsak, C. H. Righolt, and L. Klewes, Quantitative Superresolution Microscopy Reveals Differences in Nuclear DNA Organization of Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance, J. Cell. Biochem, vol.116, issue.5, pp.704-710, 2015.

P. Wu, T. Li, and R. Li, 3D genome of multiple myeloma reveals spatial genome disorganization associated with copy number variations, Nat. Commun, vol.8, 2017.

C. Pawlyn, M. F. Kaiser, and C. Heuck, The spectrum and clinical impact of epigenetic modifier mutations in myeloma, Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res, vol.22, issue.23, pp.5783-5794, 2016.

S. Mithraprabhu, A. Kalff, A. Chow, T. Khong, and A. Spencer, Dysregulated Class I histone deacetylases are indicators of poor prognosis in multiple myeloma, Epigenetics, vol.9, issue.11, pp.1511-1520, 2014.

C. Choudhary, C. Kumar, and F. Gnad, Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions, Science, vol.325, issue.5942, pp.834-840, 2009.

H. Ohguchi, T. Hideshima, and M. K. Bhasin, The KDM3A-KLF2-IRF4 axis maintains myeloma cell survival, Nat. Commun, vol.7, p.10258, 2016.

X. Wei, M. N. Calvo-vidal, and S. Chen, Germline mutations in lysine specific demethylase 1 (LSD1/KDM1A) confer susceptibility to multiple myeloma, Cancer Res, 2017.

M. Alzrigat, A. A. Párraga, and H. Jernberg-wiklund, Epigenetics in multiple myeloma: From mechanisms to therapy, Semin. Cancer Biol, 2017.

M. A. Chapman, M. S. Lawrence, and J. J. Keats, Initial genome sequencing and analysis of multiple myeloma, Nature, vol.471, issue.7339, pp.467-472, 2011.

J. Oyer, X. Huang, and Y. Zheng, Point mutation E1099K in MMSET/NSD2 enhances its methyltranferase activity and leads to altered global chromatin methylation in lymphoid malignancies, Leukemia, vol.28, issue.1, pp.198-201, 2014.

A. J. Kuo, P. Cheung, and K. Chen, NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming, Mol. Cell, vol.44, issue.4, pp.609-620, 2011.

J. Marango, M. Shimoyama, and H. Nishio, The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor, Blood, vol.111, issue.6, pp.3145-3154, 2008.

D. Min, T. Ezponda, and M. Kim, MMSET stimulates myeloma cell growth through microRNAmediated modulation of c-MYC, Leukemia, vol.27, issue.3, 2013.

I. Hajdu, A. Ciccia, S. M. Lewis, and S. J. Elledge, Wolf-Hirschhorn syndrome candidate 1 is involved in the cellular response to DNA damage, Proc. Natl. Acad. Sci. U. S. A, vol.108, issue.32, pp.13130-13134, 2011.

M. Y. Shah, E. Martinez-garcia, and J. M. Phillip, MMSET/WHSC1 enhances DNA damage repair leading to an increase in resistance to chemotherapeutic agents, Oncogene, 2016.

T. Ezponda, D. Dupéré-richer, and C. M. Will, UTX/KDM6A Loss Enhances the Malignant Phenotype of Multiple Myeloma and Sensitizes Cells to EZH2 inhibition, Cell Rep, vol.21, issue.3, pp.628-640, 2017.

G. #^^!-313.-van-haaften, G. L. Dalgliesh, and H. Davies, Somatic mutations of the histone H3K27 demethylase, UTX, in human cancer, Nat. Genet, vol.41, issue.5, pp.521-523, 2009.

J. Van-der-meulen, F. Speleman, V. Vlierberghe, and P. , The H3K27me3 demethylase UTX in normal development and disease, Epigenetics, vol.9, issue.5, pp.658-668, 2014.

F. Zhan, J. Hardin, and B. Kordsmeier, Global gene expression profiling of multiple myeloma, monoclonal gammopathy of undetermined significance, and normal bone marrow plasma cells, Blood, vol.99, issue.5, pp.1745-1757, 2002.

A. Kalushkova, M. Fryknäs, and M. Lemaire, Polycomb Target Genes Are Silenced in Multiple Myeloma, PLoS ONE, vol.5, issue.7, p.11483, 2010.

C. Pawlyn, M. D. Bright, and A. F. Buros, Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control, Blood Cancer J, vol.7, issue.3, p.549, 2017.

P. Agarwal, M. Alzrigat, and A. A. Párraga, Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target, Oncotarget, vol.7, issue.6, p.6809, 2016.

P. A. Croonquist and B. Van-ness, The polycomb group protein enhancer of zeste homolog 2 (EZH2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype, Oncogene, vol.24, issue.41, pp.6269-6280, 2005.

P. A. Croonquist, Gene profiling of a myeloma cell line reveals similarities and unique signatures among IL-6 response, N-ras-activating mutations, and coculture with bone marrow stromal cells, Blood, vol.102, issue.7, pp.2581-2592, 2003.

M. Nara, K. Teshima, and A. Watanabe, Bortezomib Reduces the Tumorigenicity of Multiple Myeloma via Downregulation of Upregulated Targets in Clonogenic Side Population Cells, PLoS ONE, vol.8, issue.3, p.56954, 2013.

H. Hernando, K. A. Gelato, and R. Lesche, EZH2 Inhibition Blocks Multiple Myeloma Cell Growth through Upregulation of Epithelial Tumor Suppressor Genes, Mol. Cancer Ther, vol.15, issue.2, pp.287-298, 2016.

M. Alzrigat, A. A. Párraga, and P. Agarwal, EZH2 inhibition in multiple myeloma downregulates myeloma associated oncogenes and upregulates microRNAs with potential tumor suppressor functions, OncoTarget, 2016.

O. Rizq, N. Mimura, and M. Oshima, Dual inhibition of EZH2 and EZH1 sensitizes PRC2-dependent tumors to proteasome inhibition, Clin. Cancer Res, 2016.

F. Zhao, Y. Chen, and L. Zeng, Role of triptolide in cell proliferation, cell cycle arrest, apoptosis and histone methylation in multiple myeloma U266 cells, Eur. J. Pharmacol, vol.646, issue.1-3, pp.1-11, 2010.

T. B. Miranda, C. C. Cortez, and C. B. Yoo, DZNep is a global histone methylation inhibitor that reactivates developmental genes not silenced by DNA methylation, Mol. Cancer Ther, vol.8, issue.6, pp.1579-1588, 2009.

Z. Xie, C. Bi, and L. L. Cheong, Determinants of Sensitivity to DZNep Induced Apoptosis in Multiple Myeloma Cells, PLoS ONE, vol.6, issue.6, p.21583, 2011.

C. Bi, T. Chung, and G. Huang, Genome-wide pharmacologic unmasking identifies tumor suppressive microRNAs in multiple myeloma, Oncotarget, vol.6, issue.28, 2015.

W. Zhang, Y. E. Wang, and Y. Zhang, Global Epigenetic Regulation of MicroRNAs in Multiple Myeloma, PLoS ONE, vol.9, issue.10, p.110973, 2014.

J. Adamik, J. S. Sun, and Q. , EZH2 or HDAC1 Inhibition Reverses Multiple Myeloma-Induced Epigenetic Suppression of Osteoblast Differentiation, Mol. Cancer Res, vol.15, issue.4, pp.405-417, 2017.

C. Fang, Y. Qiao, and S. H. Mun, Cutting Edge: EZH2 Promotes Osteoclastogenesis by Epigenetic Silencing of the Negative Regulator IRF8, J. Immunol, vol.196, issue.11, pp.4452-4456, 2016.

J. Moreaux, B. Klein, and R. Bataille, A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines, Haematologica, vol.96, issue.4, pp.574-582, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00550232

M. Jourdan, K. Mahtouk, and J. Veyrune, Delineation of the roles of paracrine and autocrine interleukin-6 (IL-6) in myeloma cell lines in survival versus cell cycle. A possible model for the cooperation of myeloma cell growth factors, vol.8
URL : https://hal.archives-ouvertes.fr/inserm-00130868

M. Cives, V. Simone, O. Brunetti, V. Longo, and F. Silvestris, Novel lenalidomide-based combinations for treatment of multiple myeloma, Crit. Rev. Oncol. Hematol, vol.85, issue.1, pp.9-20, 2013.

!. #^&lt;!,

A. A. Guirguis and B. L. Ebert, Lenalidomide: deciphering mechanisms of action in myeloma, myelodysplastic syndrome and beyond, Curr. Opin. Cell Biol, vol.37, pp.61-67, 2015.

J. Fecteau, L. G. Corral, and E. M. Ghia, Lenalidomide inhibits the proliferation of CLL cells via a cereblon/p21WAF1/Cip1-dependent mechanism independent of functional p53, Blood, vol.124, issue.10, pp.1637-1644, 2014.

L. Escoubet-lozach, L. Jensen-pergakes, and K. , Pomalidomide and Lenalidomide Induce p21WAF-1 Expression in Both Lymphoma and Multiple Myeloma through a LSD1-Mediated Epigenetic Mechanism, Cancer Res, vol.69, issue.18, pp.7347-7356, 2009.

Y. X. Zhu, E. Braggio, and C. Shi, Identification of cereblon-binding proteins and relationship with response and survival after IMiDs in multiple myeloma, Blood, vol.124, issue.4, pp.536-545, 2014.

C. C. Bjorklund, L. Lu, and J. Kang, Rate of CRL4CRBN substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4, Blood Cancer J, vol.5, issue.10, p.354, 2015.

D. Y. Yang, J. H. Ren, and X. N. Guo, Lenalidomide affect expression level of cereblon protein in multiple myeloma cell line RPMI8226, Genet. Mol. Res, vol.7, 2015.

S. Sebastian, Y. X. Zhu, and E. Braggio, Multiple myeloma cells capacity to decompose H2O2 determines lenalidomide sensitivity, Blood, 2016.

L. E. Franssen, I. S. Nijhof, and S. Couto, Cereblon loss and up-regulation of c-Myc are associated with lenalidomide resistance in multiple myeloma patients, Haematologica, 2018.

Y. Kawano, . Fujiwara-s, and . Wada-n, Multiple myeloma cells expressing low levels of CD138 have an immature phenotype and reduced sensitivity to lenalidomide, Int. J. Oncol, vol.41, issue.3, pp.876-884, 2012.

M. Bhutani, Q. Zhang, and R. Friend, Investigation of a gene signature to predict response to immunomodulatory derivatives for patients with multiple myeloma: an exploratory, retrospective study using microarray datasets from prospective clinical trials, Lancet Haematol, vol.4, issue.9, pp.443-451, 2017.

Y. X. Zhu, H. Yin, and L. A. Bruins, RNA interference screening identifies lenalidomide sensitizers in multiple myeloma, including RSK2, Blood, vol.125, issue.3, pp.483-491, 2015.

N. G. Dolloff, Emerging Therapeutic Strategies for Overcoming Proteasome Inhibitor Resistance, Adv. Cancer Res, vol.127, pp.191-226, 2015.

C. T. Wallington-beddoe, M. Sobieraj-teague, B. J. Kuss, and S. M. Pitson, Resistance to proteasome inhibitors and other targeted therapies in myeloma, Br. J. Haematol, 2018.

C. Kervoëlen, La dexamethasone dans le myélome multiple : étude des mécanismes de sensibilité et impact de l'hétérogénéité moléculaire de la maladie sur la réponse, 2015.

C. Kervoëlen, E. Ménoret, and P. Gomez-bougie, Dexamethasone-induced cell death is restricted to specific molecular subgroups of multiple myeloma, Oncotarget, vol.6, issue.29, 2015.

J. Moreaux, BAFF and APRIL protect myeloma cells from apoptosis induced by interleukin 6 deprivation and dexamethasone, Blood, vol.103, issue.8, pp.3148-3157, 2004.
URL : https://hal.archives-ouvertes.fr/inserm-00129502

C. Gourzones-dmitriev, A. Kassambara, and S. Sahota, DNA repair pathways in human multiple myeloma, Cell Cycle, vol.12, issue.17, pp.2760-2773, 2013.

V. J. Spanswick, Repair of DNA interstrand crosslinks as a mechanism of clinical resistance to melphalan in multiple myeloma, Blood, vol.100, issue.1, pp.224-229, 2002.

Q. Chen, The FA/BRCA pathway is involved in melphalan-induced DNA interstrand cross-link repair and accounts for melphalan resistance in multiple myeloma cells, Blood, vol.106, issue.2, pp.698-705, 2005.

J. Xie, L. Zhang, and M. Li, Functional analysis of the involvement of apurinic/apyrimidinic endonuclease 1 in the resistance to melphalan in multiple myeloma, BMC Cancer, vol.14, p.11, 2014.

M. Sousa, K. A. Zub, and P. A. Aas, An Inverse Switch in DNA Base Excision and Strand Break Repair Contributes to Melphalan Resistance in Multiple Myeloma Cells, PLoS ONE, vol.8, issue.2, 2013.

R. Szalat, M. K. Samur, and M. Fulciniti, Nucleotide excision repair is a potential therapeutic target in multiple myeloma, Leukemia, 2017.
URL : https://hal.archives-ouvertes.fr/hal-01813384

S. Surget, E. Lemieux-blanchard, and S. Maïga, Bendamustine and melphalan kill myeloma cells similarly through reactive oxygen species production and activation of the p53 pathway and do not overcome resistance to each other, Leuk. Lymphoma, vol.55, issue.9, pp.2165-2173, 2014.

K. A. Zub, M. De-sousa, and A. Sarno, Modulation of Cell Metabolic Pathways and Oxidative Stress Signaling Contribute to Acquired Melphalan Resistance in Multiple Myeloma Cells, PLoS ONE, vol.10, issue.3, 2015.

E. Viziteu, B. Klein, and J. Basbous, RECQ1 helicase is involved in replication stress survival and drug resistance in multiple myeloma, Leukemia, vol.31, issue.10, pp.2104-2113, 2017.
URL : https://hal.archives-ouvertes.fr/hal-02352722

L. A. Hazlehurst, S. A. Enkemann, and C. A. Beam, Genotypic and Phenotypic Comparisons of de Novo and Acquired Melphalan Resistance in an Isogenic Multiple Myeloma Cell Line Model, vol.8

J. R. Mikhael, D. Dingli, and V. Roy, Management of Newly Diagnosed Symptomatic Multiple Myeloma: Updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Guidelines, Mayo Clin. Proc, vol.88, issue.4, pp.360-376, 2013.

E. Zamagni, P. Tacchetti, L. Pantani, and M. Cavo, Anti-CD38 and anti-SLAMF7: the future of myeloma immunotherapy, Expert Rev. Hematol, vol.11, issue.5, pp.423-435, 2018.

C. Varga, M. Maglio, I. M. Ghobrial, and P. G. Richardson, Current use of monoclonal antibodies in the treatment of multiple myeloma, Br. J. Haematol, 2018.

J. Krejcik, T. Casneuf, and I. S. Nijhof, Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma, Blood, vol.128, issue.3, pp.384-394, 2016.

M. Taniwaki, M. Yoshida, and Y. Matsumoto, ELOTUZUMAB FOR THE TREATMENT OF RELAPSED OR REFRACTORY MULTIPLE MYELOMA, WITH SPECIAL REFERENCE TO ITS MODES OF ACTION AND SLAMF7 SIGNALING, Mediterr. J. Hematol. Infect. Dis, vol.10, issue.1, p.2018014, 2018.

I. S. Nijhof, R. Groen, and W. A. Noort, Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib, Clin. Cancer Res, vol.21, issue.12, pp.2802-2810, 2015.

M. Köhler, C. Greil, and M. Hudecek, Current developments in immunotherapy in the treatment of multiple myeloma: Immunotherapy in Multiple Myeloma, Cancer, vol.124, issue.10, pp.2075-2085, 2018.

D. W. Sherbenou, T. M. Mark, and P. Forsberg, Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future, Clin. Lymphoma Myeloma Leuk, vol.17, issue.9, pp.545-554, 2017.

L. Boussi and R. Niesvizky, Advances in immunotherapy in multiple myeloma, Curr. Opin. Oncol, vol.29, issue.6, pp.460-466, 2017.

C. S. Chim, S. K. Kumar, and R. Z. Orlowski, Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond, Leukemia, vol.32, issue.2, pp.252-262, 2018.

I. S. Nijhof, N. Van-de-donk, S. Zweegman, and H. M. Lokhorst, Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update, Drugs, vol.78, issue.1, pp.19-37, 2018.

S. K. Kumar, B. Laplant, and W. J. Chng, Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma, Blood, vol.125, issue.3, pp.443-448, 2015.

M. D&apos;agostino, M. Salvini, A. Palumbo, A. Larocca, and F. Gay, Novel investigational drugs active as single agents in multiple myeloma, Expert Opin. Investig. Drugs, vol.26, issue.6, pp.699-711, 2017.

K. Maes, E. Menu, V. Valckenborgh, and E. , Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma, Cancers, vol.5, issue.4, pp.430-461, 2013.

J. Moreaux, T. Reme, and W. Leonard, Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors, Br. J. Cancer, vol.109, issue.3, pp.676-685, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00906782

J. Moreaux, A. Bruyer, and J. Veyrune, DNA methylation score is predictive of myeloma cell sensitivity to 5-azacitidine, Br. J. Haematol, vol.164, issue.4, pp.613-616, 2014.
URL : https://hal.archives-ouvertes.fr/inserm-00906054

J. Moreaux, T. Reme, and W. Leonard, Development of Gene Expression-Based Score to Predict Sensitivity of Multiple Myeloma Cells to DNA Methylation Inhibitors, Mol. Cancer Ther, vol.11, issue.12, pp.2685-2692, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00760269

I. A. Asangani, B. Ateeq, and Q. Cao, Characterization of the EZH2-MMSET Histone Methyltransferase Regulatory Axis in Cancer, Mol. Cell, vol.49, issue.1, pp.80-93, 2013.

R. Popovic, E. Martinez-garcia, and E. G. Giannopoulou, Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation, PLoS Genet, vol.10, issue.9, p.1004566, 2014.

!. #^v!,

K. Dimopoulos, S. Helbo, A. , F. Munch!petersen, and H. , Dual inhibition of DNMTs and EZH2 can overcome both intrinsic and acquired resistance of myeloma cells to IMiDs in a cereblon! independent manner, Mol. Oncol, vol.12, issue.2, pp.180-195, 2018.

J. Kikuchi, D. Koyama, and T. Wada, Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma, J. Clin. Invest, vol.125, issue.12, pp.4375-4390, 2015.

J. Mestas and C. Hughes, Of Mice and Not Men: Differences between Mouse and Human Immunology, J. Immunol, vol.172, issue.5, pp.2731-2738, 2004.

T. Shay, V. Jojic, and O. Zuk, Conservation and divergence in the transcriptional programs of the human and mouse immune systems, Proc. Natl. Acad. Sci, vol.110, issue.8, pp.2946-2951, 2013.

L. K. Beura, S. E. Hamilton, and K. Bi, Normalizing the environment recapitulates adult human immune traits in laboratory mice, Nature, vol.532, issue.7600, pp.512-516, 2016.

L. K. Beura, S. E. Hamilton, and K. Bi, Recapitulating adult human immune traits in laboratory mice by normalizing environment, Nature, vol.532, issue.7600, pp.512-516, 2016.

L. Tao and T. A. Reese, Making Mouse Models That Reflect Human Immune Responses, Trends Immunol, vol.38, issue.3, pp.181-193, 2017.

S. Reardon, Dirty room-mates make lab mice more useful, Nature, vol.532, issue.7599, pp.294-295, 2016.

J. Hasbold, L. M. Corcoran, D. M. Tarlinton, S. G. Tangye, and P. D. Hodgkin, Evidence from the generation of immunoglobulin G-secreting cells that stochastic mechanisms regulate lymphocyte differentiation, Nat. Immunol, vol.5, issue.1, pp.55-63, 2004.

Z. Dai, S. J. Mentch, X. Gao, S. N. Nichenametla, and J. W. Locasale, Methionine metabolism influences genomic architecture and gene expression through H3K4me3 peak width, Nat. Commun, vol.9, issue.1, 2018.

B. G. Barwick, C. D. Scharer, and R. J. Martinez, B cell activation and plasma cell differentiation are inhibited by de novo DNA methylation, Nat. Commun, vol.9, 2018.

W. J. Coker, A. Jeter, H. Schade, and Y. Kang, Plasma cell disorders in HIV-infected patients: epidemiology and molecular mechanisms, Biomark. Res, vol.1, issue.1, p.8, 2013.

H. Wu, Y. Deng, and Y. Feng, Epigenetic regulation in B-cell maturation and its dysregulation in autoimmunity, Cell. Mol. Immunol, 2018.

S. Malkiel, A. N. Barlev, Y. Atisha-fregoso, J. Suurmond, and B. Diamond, Plasma Cell Differentiation Pathways in Systemic Lupus Erythematosus, Front. Immunol, vol.9, 2018.

Q. Pan-hammarström, H. Abolhassani, and L. Hammarström, Defects in plasma cell differentiation are associated with primary immunodeficiency in human subjects, J. Allergy Clin. Immunol, vol.141, issue.4, pp.1217-1219, 2018.

P. Cheung, F. Vallania, and H. C. Warsinske, Single-Cell Chromatin Modification Profiling Reveals Increased Epigenetic Variations with, Aging. Cell, 2018.

J. Van-dongen, M. G. Nivard, and G. Willemsen, Genetic and environmental influences interact with age and sex in shaping the human methylome, Nat. Commun, vol.7, p.11115, 2016.

V. González-calle, N. Keane, E. Braggio, and R. Fonseca, Precision Medicine in Myeloma: Challenges in Defining an Actionable Approach, Clin. Lymphoma Myeloma Leuk, vol.17, issue.10, pp.621-630, 2017.

K. K. Jain, Textbook of personalized medicine, 2015.

M. B. Treppendahl, L. S. Kristensen, and K. Grønbaek, Predicting response to epigenetic therapy, J. Clin. Invest, vol.124, issue.1, pp.47-55, 2014.

A. Bruyer, K. Maes, and L. Herviou, DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells, Br. J. Cancer, vol.118, issue.8, pp.1062-1073, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01792246

C. Leung-hagesteijn, N. Erdmann, and G. Cheung, Xbp1s-Negative Tumor B Cells and Pre-Plasmablasts Mediate Therapeutic Proteasome Inhibitor Resistance in Multiple Myeloma, Cancer Cell, vol.24, issue.3, pp.289-304, 2013.

J. Dunn and S. Rao, Epigenetics and immunotherapy: The current state of play, Mol. Immunol, vol.87, pp.227-239, 2017.

S. J. Gallagher, E. Shklovskaya, and P. Hersey, Epigenetic modulation in cancer immunotherapy, Curr. Opin. Pharmacol, vol.35, pp.48-56, 2017.

S. Bugide, M. R. Green, and N. Wajapeyee, Inhibition of Enhancer of zeste homolog 2 (EZH2) induces natural killer cell-mediated eradication of hepatocellular carcinoma cells, Proc. Natl. Acad. Sci, vol.115, issue.15, pp.3509-3518, 2018.

!. #&lt;e!,

B. He, S. Xing, and C. Chen, CD8+ T Cells Utilize Highly Dynamic Enhancer Repertoires and Regulatory Circuitry in Response to Infections, Immunity, vol.45, issue.6, pp.1341-1354, 2016.

L. A. Leslie and A. Younes, Antibody-drug conjugates in hematologic malignancies, 2013.

Y. Tai, P. A. Mayes, and C. Acharya, Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma, Blood, vol.123, issue.20, pp.3128-3138, 2014.

A. Zheleznyak, M. Shokeen, and S. Achilefu, Nanotherapeutics for multiple myeloma, Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol, 1526.

C. J. References-1.-heuck, Myeloma is characterized by stage-specific alterations in DNA methylation that occur early during myelomagenesis, J. Immunol, vol.190, pp.2966-2975, 2013.

B. A. Walker, Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma, Blood, vol.117, pp.553-562, 2010.

P. W. Hollenbach, A comparison of azacitidine and decitabine activities in acute myeloid leukemia cell lines, PLoS ONE, vol.5, p.9001, 2010.

K. Maes, Epigenetic modulating agents as a new therapeutic approach in multiple myeloma, Cancers, vol.5, pp.430-461, 2013.

R. Feng, KD5170, a novel mercaptoketone-based histone deacetylase inhibitor, exerts antimyeloma effects by DNA damage and mitochondrial signaling, Mol. Cancer Ther, vol.7, pp.1494-1505, 2008.

T. Hideshima, Induction of differential apoptotic pathways in multiple myeloma cells by class-selective histone deacetylase inhibitors, Leukemia, vol.28, pp.457-460, 2013.

M. Kaiser, The effects of the histone deacetylase inhibitor valproic acid on cell cycle, growth suppression and apoptosis in multiple myeloma, Haematologica, vol.91, pp.248-251, 2006.

S. B. Khan, T. Maududi, K. Barton, J. Ayers, and S. Alkan, Analysis of histone deacetylase inhibitor, depsipeptide (FR901228), effect on multiple myeloma, Br. J. Haematol, vol.125, pp.156-161, 2004.

D. Lavelle, Y. H. Chen, M. Hankewych, and J. Desimone, Histone deacetylase inhibitors increasep21(WAF1) and induce apoptosis of human myeloma cell lines independent of decreased IL-6 receptor expression, Am. J. Hematol, vol.68, pp.170-178, 2001.

J. Minami, Histone deacetylase 3 as a novel therapeutic target in multiple myeloma, Leukemia, vol.28, pp.680-689, 2013.

C. S. Mitsiades, Transcriptional signature of histone deacetylase inhibition in multiple myeloma: biological and clinical implications, Proc. Natl. Acad. Sci. USA, vol.101, pp.540-545, 2004.

N. Mitsiades, Molecular sequelae of histone deacetylase inhibition in human malignant B cells, Blood, vol.101, pp.4055-4062, 2003.

L. Catley, NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma, Blood, vol.102, pp.2615-2622, 2003.

P. Neri, N. J. Bahlis, and S. Lonial, Panobinostat for the treatment of multiple myeloma, Expert Opin. Investig. Drugs, vol.21, pp.733-747, 2012.

P. Neri, In vivo anti-myeloma activity and modulation of gene expression profile induced by valproic acid, a histone deacetylase inhibitor, Br. J. Haematol, vol.143, pp.520-531, 2008.

Q. L. Zhang, The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis, Leukemia, vol.23, pp.1507-1514, 2009.

M. Dimopoulos, Vorinostat or placebo in combination with bortezomib in patients with multiple myeloma (VANTAGE 088): a multicentre, randomised, double-blind study, Lancet Oncol, vol.14, pp.1129-1140, 2013.

P. G. Richardson, PANORAMA 2: panobinostat in combination with bortezomib and dexamethasone in patients with relapsed and bortezomib-refractory myeloma, Blood, vol.122, pp.2331-2337, 2013.

J. P. Laubach, P. Moreau, J. F. San-miguel, and P. G. Richardson, Panobinostat for the treatment of multiple myeloma, Clin. Cancer Res, vol.21, pp.4767-4773, 2015.

P. G. Richardson, Pomalidomide, bortezomib and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma, Leukemia, vol.31, pp.2695-2701, 2017.

J. F. San-miguel, Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, doubleblind phase 3 trial, Lancet Oncol, vol.15, pp.1195-1206, 2014.

G. M. Matthews, Preclinical screening of histone deacetylase inhibitors combined with ABT-737, rhTRAIL/MD5-1 or 5-azacytidine using syngeneic Vk*MYC multiple myeloma, Cell Death Dis, vol.4, p.798, 2013.

K. Maes, In vivo treatment with epigenetic modulating agents induces transcriptional alterations associated with prognosis and immunomodulation in multiple myeloma, Oncotarget, vol.6, pp.3319-3334, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01153601

M. Bots and R. W. Johnstone, Rational combinations using HDAC inhibitors, Clin. Cancer Res, vol.15, pp.3970-3977, 2009.

T. E. Fandy, Early epigenetic changes and DNA damage do not predict clinical response in an overlapping schedule of 5-azacytidine and entinostat in patients with myeloid malignancies, Blood, vol.114, pp.2764-2773, 2009.

R. A. Juergens, Combination epigenetic therapy has efficacy in patients with refractory advanced non-small cell lung cancer, Cancer Discov, vol.1, pp.598-607, 2011.

J. Moreaux, Development of gene expression-based score to predict sensitivity of multiple myeloma cells to DNA methylation inhibitors, Mol. Cancer Ther, vol.11, pp.2685-2692, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00760269

J. Moreaux, Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors, Br. J. Cancer, vol.109, pp.676-685, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00906782

Z. J. Gu, Agonist anti-gp130 transducer monoclonal antibodies are human myeloma cell survival and growth factors, Leukemia, vol.14, pp.188-197, 2000.

J. Moreaux, TACI expression is associated with a mature bone marrow plasma cell signature and C-MAF overexpression in human myeloma cell lines, Haematologica, vol.92, pp.803-811, 2007.
URL : https://hal.archives-ouvertes.fr/inserm-00162002

J. Moreaux, A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines, Haematologica, vol.96, pp.574-582, 2011.
URL : https://hal.archives-ouvertes.fr/inserm-00550232

C. Rebouissou, A gp130 interleukin-6 transducer-dependent SCID model of human multiple myeloma, Blood, vol.91, pp.4727-4737, 1998.

K. Tarte, Induced expression of B7-1 on myeloma cells following retroviral gene transfer results in tumor-specific recognition by cytotoxic T cells, J. Immunol, vol.163, pp.514-524, 1999.

X. G. Zhang, Reproducible obtaining of human myeloma cell lines as a model for tumor stem cell study in human multiple myeloma, Blood, vol.83, pp.3654-3663, 1994.

D. Hose, Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma, Haematologica, vol.96, pp.87-95, 2011.

J. De-vos, Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays, Oncogene, vol.21, pp.6848-6857, 2002.

B. Barlogie, Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies, Blood, vol.107, pp.2633-2638, 2006.

A. Kassambara, Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma, Haematologica, vol.97, pp.622-630, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00727008

W. Xiong, An analysis of the clinical and biologic significance of TP53 loss and the identification of potential novel transcriptional targets of TP53 in multiple myeloma, Blood, vol.112, pp.4235-4246, 2008.

G. Mulligan, Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib, Blood, vol.109, pp.3177-3188, 2007.

, HDACi/DNMTi induced reprogramming of myeloma cells A Bruyer et al

M. Jourdan, Characterization of a transitional preplasmablast population in the process of human B cell to plasma cell differentiation, J. Immunol, vol.187, pp.3931-3941, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00743965

M. Jourdan, An in vitro model of differentiation of memory B cells into plasmablasts and plasma cells including detailed phenotypic and molecular characterization, Blood, vol.114, pp.5173-5181, 2009.
URL : https://hal.archives-ouvertes.fr/inserm-00446133

G. Heller, Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells, Cancer Res, vol.68, pp.44-54, 2008.

K. Mahtouk, An inhibitor of the EGF receptor family blocks myeloma cell growth factor activity of HB-EGF and potentiates dexamethasone or anti-IL-6 antibody-induced apoptosis, Blood, vol.103, pp.1829-1837, 2004.
URL : https://hal.archives-ouvertes.fr/inserm-00130207

X. Cui and G. A. Churchill, Statistical tests for differential expression in cDNA microarray experiments, Genome Biol, vol.4, p.210, 2003.

A. Kassambara, GenomicScape: an easy-to-use web tool for gene expression data analysis. Application to investigate the molecular events in the differentiation of B cells into plasma cells, PLoS Comput. Biol, vol.11, p.1004077, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01112225

A. Subramanian, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proc. Natl. Acad. Sci. USA, vol.102, pp.15545-15550, 2005.

M. B. Eisen, P. T. Spellman, P. O. Brown, and D. Botstein, Cluster analysis and display of genome-wide expression patterns, Proc. Natl. Acad. Sci. USA, vol.95, pp.14863-14868, 1998.

M. Jourdan, Differential effects of lenalidomide during plasma cell differentiation, Oncotarget, vol.7, pp.28096-28111, 2016.
URL : https://hal.archives-ouvertes.fr/hal-01355076

F. Zhan, The molecular classification of multiple myeloma, Blood, vol.108, pp.2020-2028, 2006.

T. Hothorn and B. Lausen, On the exact distribution of maximally selected rank statistics, Comput. Stat. Data Anal, vol.43, pp.121-137, 2003.

J. D. Shaughnessy, A validated gene expression model of high-risk multiple myeloma is defined by deregulated expression of genes mapping to chromosome 1, Blood, vol.109, pp.2276-2284, 2007.

O. Decaux, Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myelome, J. Clin. Oncol, vol.26, pp.4798-4805, 2008.

T. Reme, D. Hose, C. Theillet, and B. Klein, Modeling risk stratification in human cancer, Bioinformatics, vol.29, pp.1149-1157, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00806666

H. Cedar and Y. Bergman, Linking DNA methylation and histone modification: patterns and paradigms, Nat. Rev. Genet, vol.10, pp.295-304, 2009.

L. A. Humphries, Pro-apoptotic TP53 homolog TAp63 is repressed via epigenetic silencing and B-cell receptor signalling in chronic lymphocytic leukaemia, Br. J. Haematol, vol.163, pp.590-602, 2013.

D. G. Hildebrand, IkappaBzeta is a transcriptional key regulator of CCL2/ MCP-1, J. Immunol, vol.190, pp.4812-4820, 2013.

N. Bolli, Heterogeneity of genomic evolution and mutational profiles in multiple myeloma, Nat. Commun, vol.5, p.2997, 2014.

J. G. Lohr, Widespread genetic heterogeneity in multiple myeloma: implications for targeted therapy, Cancer Cell, vol.25, pp.91-101, 2014.

B. A. Walker, Mutational spectrum, copy number changes, and outcome: results of a sequencing study of patients with newly diagnosed myeloma, J. Clin. Oncol, vol.33, pp.3911-3920, 2015.

G. Totzke, A novel member of the IkappaB family, human IkappaB-zeta, inhibits transactivation of p65 and its DNA binding, J. Biol. Chem, vol.281, pp.12645-12654, 2006.

Z. Wu, Nuclear protein IkappaB-zeta inhibits the activity of STAT3, Biochem Biophys. Res Commun, vol.387, pp.348-352, 2009.

S. Derenne, Antisense strategy shows that Mcl-1 rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells, Blood, vol.100, pp.194-199, 2002.

M. Jourdan, A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells, Oncogene, vol.22, pp.2950-2959, 2003.
URL : https://hal.archives-ouvertes.fr/inserm-00130855

E. Braggio, Methylation status of nine tumor suppressor genes in multiple myeloma, Int J. Hematol, vol.91, pp.87-96, 2010.

M. V. Mateos, Methylation is an inactivating mechanism of the p16 gene in multiple myeloma associated with high plasma cell proliferation and short survival, Br. J. Haematol, vol.118, pp.1034-1040, 2002.

S. Takada, Methylation status of fragile histidine triad (FHIT) gene and its clinical impact on prognosis of patients with multiple myeloma, Eur. J. Haematol, vol.75, pp.505-510, 2005.

M. E. Harris, Regulation of histone mRNA in the unperturbed cell cycle: evidence suggesting control at two posttranscriptional steps, Mol. Cell Biol, vol.11, pp.2416-2424, 1991.

A. L. Shaffer, IRF4 addiction in multiple myeloma, Nature, vol.454, pp.226-231, 2008.

S. Iida, Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma, Nat. Genet, vol.17, pp.226-230, 1997.

J. Loven, Selective inhibition of tumor oncogenes by disruption of superenhancers, Cell, vol.153, pp.320-334, 2013.

J. Kronke, Lenalidomide causes selective degradation of IKZF1 and IKZF3 in multiple myeloma cells, Science, vol.343, pp.301-305, 2014.

G. Lu, The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins, Science, vol.343, pp.305-309, 2014.

S. V. Rajkumar, Treatment of multiple myeloma, Nat Rev Clin Oncol, vol.10, issue.8, pp.479-491, 2011.

O. Landgren, R. A. Kyle, and R. M. Pfeiffer, Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study, Blood, vol.113, issue.22, pp.5412-5417, 2009.

S. B. Baylin, DNA methylation and gene silencing in cancer, Nat Clin Pract, vol.15

, Oncol, vol.2, issue.1, pp.4-11, 2005.

Y. Kondo, Epigenetic cross-talk between DNA methylation and histone modifications in human cancers, Yonsei Med J, vol.50, issue.4, pp.455-463, 2009.

C. J. Heuck, J. Mehta, and T. Bhagat, Myeloma is characterized by stage-specific alterations in DNA methylation that occur early during myelomagenesis, J Immunol, vol.20, issue.6, pp.2966-2975, 2013.

B. A. Walker, C. P. Wardell, and L. Chiecchio, Aberrant global methylation patterns affect the molecular pathogenesis and prognosis of multiple myeloma

M. F. Kaiser, D. C. Johnson, and P. Wu, Global methylation analysis identifies prognostically important epigenetically inactivated tumour suppressor genes in multiple 25 myeloma, Blood, 2013.

K. Maes, E. Menu, E. Van-valckenborgh, I. Van-riet, K. Vanderkerken et al.,

E. Bruyne, Epigenetic Modulating Agents as a New Therapeutic Approach in Multiple Myeloma, Cancers, vol.5, issue.2, pp.430-461, 2013.

P. Neri, N. J. Bahlis, and S. Lonial, Panobinostat for the treatment of multiple 30 myeloma, Expert Opin Investig Drugs, vol.21, issue.5, pp.733-747, 2012.

P. Neri, P. Tagliaferri, D. Martino, and M. T. , In vivo anti-myeloma activity and modulation of gene expression profile induced by valproic acid, a histone deacetylase inhibitor, Br J Haematol, 2008.

J. Minami, R. Suzuki, and R. Mazitschek, Induction of differential apoptotic pathways in multiple myeloma cells by class-selective histone deacetylase inhibitors, Leukemia. 2013, vol.12

. Leukemia, , 2013.

Q. L. Zhang, L. Wang, and Y. W. Zhang, The proteasome inhibitor bortezomib interacts synergistically with the histone deacetylase inhibitor suberoylanilide hydroxamic acid to induce T-leukemia/lymphoma cells apoptosis, Leukemia, vol.23, issue.8, pp.2331-2337, 2009.

M. Dimopoulos, D. S. Siegel, and S. Lonial, Panobinostat plus bortezomib and 15 dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial, Lancet Oncol, vol.14, issue.11, pp.1195-1206, 2013.

J. Moreaux, T. Reme, and W. Leonard, Gene expression-based prediction of myeloma cell sensitivity to histone deacetylase inhibitors, Br J Cancer, vol.109, issue.3, p.18, 2013.
URL : https://hal.archives-ouvertes.fr/inserm-00906782

J. Moreaux, T. Reme, and W. Leonard, Development of gene expression-based score to predict sensitivity of multiple myeloma cells to DNA methylation inhibitors, Mol Cancer Ther, vol.11, issue.12, pp.2685-2692, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00760269

D. B. Beck, H. Oda, S. S. Shen, and D. Reinberg, PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription

, Genes Dev, vol.26, issue.4, pp.325-337, 2012.

J. Brustel, M. Tardat, O. Kirsh, C. Grimaud, and E. Julien, Coupling mitosis to DNA replication: the emerging role of the histone H4-lysine 20 methyltransferase PR-Set7, Trends Cell Biol, vol.21, issue.8, pp.452-460, 2011.
URL : https://hal.archives-ouvertes.fr/hal-02193483

S. Jorgensen, G. Schotta, and C. S. Sorensen, Histone H4 lysine 20 methylation: key 30 player in epigenetic regulation of genomic integrity, Nucleic Acids Res, vol.41, issue.5, pp.2797-2806, 2013.

X. Shi, I. Kachirskaia, and H. Yamaguchi, Modulation of p53 function by SET8-mediated methylation at lysine 382. Molecular cell, vol.27, pp.636-646, 2007.

G. K. Dhami, H. Liu, and M. Galka, Histone lysine methyltransferase SETD8 promotes carcinogenesis by deregulating PCNA expression, Molecular cell, vol.50, issue.4, p.3217, 2012.

I. Koturbash, N. E. Simpson, F. A. Beland, and I. P. Pogribny, Alterations in histone H4

, lysine 20 methylation: implications for cancer detection and prevention, Antioxid Redox Signal, vol.17, issue.2, pp.365-374, 2012.

D. Hose, T. Reme, and T. Hielscher, Proliferation is a central independent prognostic factor and target for personalized and risk-adapted treatment in multiple myeloma

, Haematologica, vol.96, issue.1, pp.87-95, 2011.

J. De-vos, T. Thykjaer, and K. Tarte, Comparison of gene expression profiling between malignant and normal plasma cells with oligonucleotide arrays, Oncogene, vol.21, issue.44, pp.6848-6857, 2002.

B. Barlogie, G. Tricot, and E. Rasmussen, Total therapy 2 without thalidomide 15 in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies, Blood, vol.107, issue.7, pp.2633-2638, 2006.

A. Kassambara, D. Hose, and J. Moreaux, Genes with a spike expression are clustered in chromosome (sub)bands and spike (sub)bands have a powerful prognostic value in patients with multiple myeloma, Haematologica, vol.97, issue.4, p.30, 2012.
URL : https://hal.archives-ouvertes.fr/inserm-00727008