F. Lille, I. Jean-pierre-aubert-research-centre, and . U1172, Division of Pediatric Hematology/Oncology, Children's Hospital, Harvard Medical School

I. M. Ghobrial, Medical Oncology, Dana-Farber Cancer Institute

F. Campigotto-7 and K. Z. , Salem 1 , Daisy Huynh 1 , Siobhan V. Glavey 1 , Bradley Rivotto 1

. Lille, I. France, and . Umr-s1172, France; 4 Division of Hematology and Oncology

. France, Dana-Farber Cancer Institute, Harvard Medical School, Biostatistics and Computational Biology, vol.7, issue.8

I. M. Ghobrial, edu Salomon Manier, salomon_manier@dfci.harvard.edu *These authors contributed equally to this work REFERENCES 1. Palumbo A, Anderson K. Multiple myeloma, The New England journal of medicine, vol.364, pp.1046-60, 2011.

H. Ludwig, V. Bolejack, and J. Crowley, Survival and Years of Life Lost in Different Age Cohorts of Patients With Multiple Myeloma, Journal of Clinical Oncology, vol.28, issue.9, pp.1599-605, 2010.
DOI : 10.1200/JCO.2009.25.2114

P. Greipp, S. Miguel, J. Durie, and B. , International Staging System for Multiple Myeloma, Journal of Clinical Oncology, vol.23, issue.15, pp.3412-3432, 2005.
DOI : 10.1200/JCO.2005.04.242

A. Palumbo, S. Rajkumar, and M. Dimopoulos, Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma, Leukemia, vol.305, issue.2, pp.414-437, 2008.
DOI : 10.1056/NEJMoa025313

A. Vital, Paraproteinemic Neuropathies, Brain Pathology, vol.50, issue.Suppl. VII, pp.399-407, 2001.
DOI : 10.1097/00005072-199109000-00009

S. Rajkumar, M. Dimopoulos, and A. Palumbo, International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma, The Lancet Oncology, vol.15, issue.12, pp.538-586, 2014.
DOI : 10.1016/S1470-2045(14)70442-5

R. Kyle and S. Rajkumar, Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma, Leukemia, vol.22, issue.1, pp.3-9, 2009.
DOI : 10.1038/leu.2008.291

A. Palumbo, H. Avet-loiseau, and S. Oliva, Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group, Journal of Clinical Oncology, vol.33, issue.26, pp.2863-2872, 2015.
DOI : 10.1200/JCO.2015.61.2267

R. Kyle, B. Durie, and S. Rajkumar, Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management, Leukemia, vol.102, issue.6, pp.1121-1128, 2010.
DOI : 10.1182/blood-2007-08-108357

M. Mateos, M. Hernandez, and P. Giraldo, Lenalidomide plus Dexamethasone for High-Risk Smoldering Multiple Myeloma, New England Journal of Medicine, vol.369, issue.5, pp.438-485, 2013.
DOI : 10.1056/NEJMoa1300439

A. Stewart, P. Richardson, and J. San-miguel, How I treat multiple myeloma in younger patients, Blood, vol.114, issue.27, pp.5436-5479, 2009.
DOI : 10.1182/blood-2009-07-204651
URL : http://www.bloodjournal.org/content/bloodjournal/114/27/5436.full.pdf

M. Attal, J. Harousseau, and A. Stoppa, A Prospective, Randomized Trial of Autologous Bone Marrow Transplantation and Chemotherapy in Multiple Myeloma, New England Journal of Medicine, vol.335, issue.2
DOI : 10.1056/NEJM199607113350204

M. Ladetto, G. Pagliano, and S. Ferrero, Major Tumor Shrinking and Persistent Molecular Remissions After Consolidation With Bortezomib, Thalidomide, and Dexamethasone in Patients With Autografted Myeloma, Journal of Clinical Oncology, vol.28, issue.12, pp.2077-84, 2010.
DOI : 10.1200/JCO.2009.23.7172

J. Harousseau, M. Attal, and H. Avet-loiseau, The role of complete response in multiple myeloma, Blood, vol.114, issue.15, pp.3139-3185, 2009.
DOI : 10.1182/blood-2009-03-201053

M. Dimopoulos, P. Richardson, and R. Schlag, VMP (Bortezomib, Melphalan, and Prednisone) Is Active and Well Tolerated in Newly Diagnosed Patients With Multiple Myeloma With Moderately Impaired Renal Function, and Results in Reversal of Renal Impairment: Cohort Analysis of the Phase III VISTA Study, Journal of Clinical Oncology, vol.27, issue.36, pp.6086-93, 2009.
DOI : 10.1200/JCO.2009.22.2232

L. Benboubker, M. Dimopoulos, and A. Dispenzieri, Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma, New England Journal of Medicine, vol.371, issue.10, pp.906-923, 2014.
DOI : 10.1056/NEJMoa1402551

M. Dimopoulos, A. Oriol, and H. Nahi, Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma, New England Journal of Medicine, vol.375, issue.14, pp.1319-1350, 2016.
DOI : 10.1056/NEJMoa1607751

S. Lonial, R. Vij, and J. Harousseau, Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma, Journal of Clinical Oncology, vol.30, issue.16
DOI : 10.1200/JCO.2011.37.2649

O. Landgren, R. Kyle, and R. Pfeiffer, Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study, Blood, vol.113, issue.22, pp.5412-5419, 2009.
DOI : 10.1182/blood-2008-12-194241

B. Weiss, J. Abadie, P. Verma, R. Howard, and W. Kuehl, A monoclonal gammopathy precedes multiple myeloma in most patients, Blood, vol.113, issue.22, pp.5418-5440, 2009.
DOI : 10.1182/blood-2008-12-195008

R. Kyle, T. Therneau, and S. Rajkumar, A Long-Term Study of Prognosis in Monoclonal Gammopathy of Undetermined Significance, New England Journal of Medicine, vol.346, issue.8, pp.564-573, 2002.
DOI : 10.1056/NEJMoa01133202

W. Chng, G. Huang, and T. Chung, Clinical and biological implications of MYC activation: a common difference between MGUS and newly diagnosed multiple myeloma, Leukemia, vol.19, issue.6, pp.1026-1061, 2011.
DOI : 10.1038/nature07968

M. Chesi, D. Robbiani, and M. Sebag, AID-dependent activation of a MYC transgene induces multiple myeloma in a conditional mouse model of post-germinal center malignancies APOBEC family mutational signatures are associated with poor prognosis translocations in multiple myeloma Rearrangements of the c-myc oncogene are present in 15% of primary human multiple myeloma tumors, Cancer cell Nat Commun Blood, vol.13698, issue.27, pp.167-8069973082, 2001.

Y. Shou, M. Martelli, and A. Gabrea, Diverse karyotypic abnormalities of the c-myc locus associated with c-myc dysregulation and tumor progression in multiple myeloma, Proceedings of the National Academy of Sciences, vol.18, issue.2, pp.228-261, 2000.
DOI : 10.1016/0165-4608(85)90066-4

M. Affer, M. Chesi, and W. Chen, Promiscuous MYC locus rearrangements hijack enhancers but mostly super-enhancers to dysregulate MYC expression in multiple myeloma, Leukemia, vol.92, issue.8, pp.1725-1760, 2014.
DOI : 10.1182/blood-2006-08-040410

D. Carrasco, G. Tonon, and Y. Huang, High-resolution genomic profiles define distinct clinico-pathogenetic subgroups of multiple myeloma patients, Cancer Cell, vol.9, issue.4, pp.313-338, 2006.
DOI : 10.1016/j.ccr.2006.03.019

H. Avet-loiseau, C. Li, and F. Magrangeas, Prognostic Significance of Copy-Number Alterations in Multiple Myeloma, Journal of Clinical Oncology, vol.27, issue.27, pp.4585-90, 2009.
DOI : 10.1200/JCO.2008.20.6136

L. Lopez-corral, M. Sarasquete, and S. Bea, SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status, Leukemia, vol.58, issue.12
DOI : 10.1016/j.canlet.2005.07.041

S. Manier, K. Salem, J. Park, D. Landau, G. Getz et al., Genomic complexity of multiple myeloma and its clinical implications Nature reviews Clinical oncology 2016 Clinical and biological significance of RAS mutations in multiple myeloma, Ras enhances Myc protein stability, pp.2280-2284, 2008.

R. Sears, F. Nuckolls, E. Haura, Y. Taya, K. Tamai et al., Multiple Rasdependent phosphorylation pathways regulate Myc protein stability, Mol Cell Genes Dev, vol.314, issue.36, pp.169-792501, 1999.
DOI : 10.1101/gad.836800
URL : http://genesdev.cshlp.org/content/14/19/2501.full.pdf

H. Mittrucker, T. Matsuyama, and A. Grossman, Requirement for the Transcription Factor LSIRF/IRF4 for Mature B and T Lymphocyte Function, Science, vol.275, issue.5299, pp.540-543, 1997.
DOI : 10.1126/science.275.5299.540

A. Shaffer, N. Emre, and L. Lamy, IRF4 addiction in multiple myeloma, Nature, vol.403, issue.7201, pp.226-257, 2008.
DOI : 10.4049/jimmunol.174.5.2573
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2542904/pdf

D. Dominguez-sola, C. Ying, and C. Grandori, Non-transcriptional control of DNA replication by c-Myc, Nature, vol.192, issue.7152, pp.445-51, 2007.
DOI : 10.1128/MCB.17.1.100

D. Felsher and J. Bishop, Transient excess of MYC activity can elicit genomic instability and tumorigenesis, Proceedings of the National Academy of Sciences, vol.57, issue.20, pp.3940-3944, 1999.
DOI : 10.1038/386623a0

K. Zeller, X. Zhao, and C. Lee, Global mapping of c-Myc binding sites and target gene networks in human B cells, Proceedings of the National Academy of Sciences, vol.25, issue.12, pp.17834-17843, 2006.
DOI : 10.1038/sj.emboj.7601152

T. Kress, A. Sabo, and B. Amati, MYC: connecting selective transcriptional control to global RNA production, Nature Reviews Cancer, vol.4, issue.10, pp.593-607, 2015.
DOI : 10.1101/cshperspect.a014191

C. Lin, J. Loven, and P. Rahl, Transcriptional Amplification in Tumor Cells with Elevated c-Myc, Cell, vol.151, issue.1, pp.56-67, 2012.
DOI : 10.1016/j.cell.2012.08.026
URL : https://doi.org/10.1016/j.cell.2012.08.026

Z. Nie, G. Hu, and G. Wei, c-Myc Is a Universal Amplifier of Expressed Genes in Lymphocytes and Embryonic Stem Cells, Cell, vol.151, issue.1, pp.68-79, 2012.
DOI : 10.1016/j.cell.2012.08.033

A. Sabo, T. Kress, and M. Pelizzola, Selective transcriptional regulation by Myc in cellular growth control and lymphomagenesis, Nature, vol.23, issue.7510, pp.488-92, 2014.
DOI : 10.1038/sj.emboj.7600279

H. Christofk, V. Heiden, M. Harris, and M. , The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth, Nature, vol.3, issue.7184, pp.230-233, 2008.
DOI : 10.1038/nature06734

C. David, M. Chen, M. Assanah, P. Canoll, J. Manley et al., HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis, Nature Nature, vol.463523, pp.364-896, 2010.

A. Arabi, S. Wu, and K. Ridderstrale, c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription, Nature Cell Biology, vol.115, issue.3, pp.303-313, 2005.
DOI : 10.1073/pnas.95.23.13887

C. Grandori, N. Gomez-roman, and Z. Felton-edkins, c-Myc binds to human ribosomal DNA and stimulates transcription of rRNA genes by RNA polymerase I, Nature Cell Biology, vol.6, issue.3, pp.311-319, 2005.
DOI : 10.1038/nrm1551

M. Pourdehnad, M. Truitt, I. Siddiqi, G. Ducker, K. Shokat et al., Myc and mTOR converge on a common node in protein synthesis control that confers synthetic lethality in Myc-driven cancers, Proceedings of the National Academy of Sciences, vol.376, issue.6538, pp.11988-93, 2013.
DOI : 10.1038/376352a0

A. Gingras, B. Raught, and S. Gygi, Hierarchical phosphorylation of the translation inhibitor 4E-BP1 Analysis of C-MYC function in normal cells via conditional gene-targeted mutation, Genes Dev Immunity, vol.1514, pp.2852-64, 2001.

T. Prathapam, S. Tegen, T. Oskarsson, A. Trumpp, and G. Martin, Activated Src abrogates the Myc requirement for the G0

M. Mateyak, A. Obaya, and J. Sedivy, c-Myc Regulates Cyclin D-Cdk4 and -Cdk6 Activity but Affects Cell Cycle Progression at Multiple Independent Points, Molecular and Cellular Biology, vol.19, issue.7, pp.4672-83, 1999.
DOI : 10.1128/MCB.19.7.4672
URL : http://europepmc.org/articles/pmc84265?pdf=render

E. Santoni-rugiu, J. Falck, N. Mailand, J. Bartek, and J. Lukas, Involvement of Myc Activity in a G1/S-Promoting Mechanism Parallel to the pRb/E2F Pathway, Molecular and Cellular Biology, vol.20, issue.10, pp.3497-509, 2000.
DOI : 10.1128/MCB.20.10.3497-3509.2000

G. Leone, R. Sears, and E. Huang, Myc Requires Distinct E2F Activities to Induce S Phase and Apoptosis, Molecular Cell, vol.8, issue.1, pp.105-118, 2001.
DOI : 10.1016/S1097-2765(01)00275-1
URL : https://doi.org/10.1016/s1097-2765(01)00275-1

J. Vlach, S. Hennecke, K. Alevizopoulos, D. Conti, and B. Amati, Growth arrest by the cyclin-dependent kinase inhibitor p27Kip1 is abrogated by c-Myc, EMBO J, vol.15, pp.6595-604, 1996.

C. Martins and A. Berns, Loss of p27Kip1 but not p21Cip1 decreases survival and synergizes with MYC in murine lymphomagenesis, The EMBO Journal, vol.21, issue.14, pp.3739-3787, 2002.
DOI : 10.1093/emboj/cdf364

A. Carrano, E. Eytan, A. Hershko, P. Mhagan, R. Ohh et al., SKP2 is required for ubiquitinmediated degradation of the CDK inhibitor p27 Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression, Nat Cell Biol Genes Dev, vol.114, issue.61, pp.193-92185, 1999.

P. Gao, I. Tchernyshyov, and T. Chang, c-Myc suppression of miR-23a/b enhances mitochondrial glutaminase expression and glutamine metabolism, Nature, vol.12, issue.7239, pp.762-767, 2009.
DOI : 10.1038/nature07823

D. Wise, R. Deberardinis, and A. Mancuso, Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction, Proceedings of the National Academy of Sciences, vol.276, issue.34
DOI : 10.1074/jbc.M103890200
URL : http://www.pnas.org/content/105/48/18782.full.pdf

Z. Stine, Z. Walton, B. Altman, A. Hsieh, C. Dang et al., MYC, Metabolism, and Cancer, Cancer Discovery, vol.5, issue.10, pp.1024-1063, 2015.
DOI : 10.1158/2159-8290.CD-15-0507
URL : http://cancerdiscovery.aacrjournals.org/content/candisc/5/10/1024.full.pdf

S. Lowe, E. Cepero, and G. Evan, Intrinsic tumour suppression, Nature, vol.35, issue.7015, pp.307-322, 2004.
DOI : 10.1080/07853890310017152

J. Martin-subero, M. Odero, and R. Hernandez, Amplification of IGH/MYC fusion in clinically aggressive IGH/BCL2-positive germinal center B-cell lymphomas

S. Knezevich, O. Ludkovski, and C. Salski, Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas, Leukemia, vol.101, issue.4, pp.659-63, 2005.
DOI : 10.1093/ajcp/101.5.587

J. Adams, A. Harris, and C. Pinkert, The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice, Nature, vol.77, issue.6046, pp.533-541, 1985.
DOI : 10.1128/MCB.2.6.617

A. Strasser, A. Harris, M. Bath, and C. S. , Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2, Nature, vol.348, issue.6299, pp.331-334, 1990.
DOI : 10.1038/348331a0

A. Letai, M. Sorcinelli, C. Beard, and S. Korsmeyer, Antiapoptotic BCL-2 is required for maintenance of a model leukemia, Cancer Cell, vol.6, issue.3, pp.241-250, 2004.
DOI : 10.1016/j.ccr.2004.07.011

S. Casey, L. Tong, and Y. Li, MYC regulates the antitumor immune response through CD47 and PD-L1, Science, vol.18, issue.19, pp.227-258, 2016.
DOI : 10.1158/1078-0432.CCR-12-0372
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4940030/pdf

T. Holien, T. Vatsveen, H. Hella, A. Waage, and A. Sundan, Addiction to c-MYC in multiple myeloma, Blood, vol.120, issue.12, pp.2450-2453, 2012.
DOI : 10.1182/blood-2011-08-371567
URL : http://www.bloodjournal.org/content/bloodjournal/120/12/2450.full.pdf

N. Snead, X. Wu, and A. Li, Molecular basis for improved gene silencing by

J. Hart, T. Roberts, M. Weinberg, K. Morris, and P. Vogt, MYC regulates the noncoding transcriptome, Oncotarget, vol.5, pp.12543-54, 2014.
DOI : 10.18632/oncotarget.3033
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350361/pdf

D. Stellas, M. Szabolcs, and S. Koul, Therapeutic Effects of an Anti-Myc Drug on Mouse Pancreatic Cancer, JNCI: Journal of the National Cancer Institute, vol.16, issue.4, 2014.
DOI : 10.1016/j.semcancer.2006.07.015

J. Delmore, G. Issa, and M. Lemieux, BET Bromodomain Inhibition as??a Therapeutic Strategy to Target c-Myc, Cell, vol.146, issue.6, pp.904-921, 2011.
DOI : 10.1016/j.cell.2011.08.017
URL : https://doi.org/10.1016/j.cell.2011.08.017

S. Amorim, A. Stathis, and M. Gleeson, Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study, The Lancet Haematology, vol.3, issue.4, pp.196-204, 2016.
DOI : 10.1016/S2352-3026(16)00021-1

B. Inhibitor, CPI-0610) of the Bromodomain and Extra-Terminal (BET) Family as a Candidate for Human Clinical Trials, J Med Chem, vol.59, pp.1330-1339, 2016.

K. Siu, J. Ramachandran, and A. Yee, Preclinical activity of CPI-0610, a novel small-molecule bromodomain and extra-terminal protein inhibitor in the therapy of multiple myeloma, Leukemia, vol.30, issue.8, 2017.
DOI : 10.1200/JCO.2011.40.6967

P. Mccarthy, K. Owzar, and C. Hofmeister, Lenalidomide after stem-cell transplantation for multiple myeloma Continuous lenalidomide treatment for newly diagnosed multiple myeloma, N Engl J Med N Engl J Med, vol.366366, issue.81, pp.1770-811759, 2012.

J. Kronke, N. Udeshi, and A. Narla, Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells, Science, vol.106, issue.12, pp.301-306, 2014.
DOI : 10.1073/pnas.0900191106

G. Lu, R. Middleton, and H. Sun, The Myeloma Drug Lenalidomide Promotes the Cereblon-Dependent Destruction of Ikaros Proteins, Science, vol.153, issue.3, pp.305-314, 2014.
DOI : 10.1016/j.cell.2013.03.036

T. Hsu, L. Simon, and N. Neill, The spliceosome is a therapeutic vulnerability in MYC-driven cancer, Nature, vol.525, issue.7569, pp.384-392, 2015.
DOI : 10.1101/gr.143586.112

N. Howlader, A. Noone, M. Yu, and K. Cronin, Use of Imputed Population-based Cancer Registry Data as a Method of Accounting for Missing Information: Application to Estrogen Receptor Status for Breast Cancer, American Journal of Epidemiology, vol.19, issue.1, pp.347-56, 2012.
DOI : 10.1158/1055-9965.EPI-09-0807

G. Morgan, B. Walker, and F. Davies, The genetic architecture of multiple myeloma, Nature Reviews Cancer, vol.214, issue.5, pp.335-383, 2012.
DOI : 10.1002/path.2279

J. Mertz, A. Conery, and B. Bryant, Targeting MYC dependence in cancer by inhibiting BET bromodomains, Proceedings of the National Academy of Sciences, vol.107, issue.20, pp.16669-74, 2011.
DOI : 10.1016/S0065-230X(10)07006-5
URL : http://www.pnas.org/content/108/40/16669.full.pdf

B. Reinhart, F. Slack, and M. Basson, The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans, Nature, vol.12, issue.6772, pp.901-907, 2000.
DOI : 10.1093/nar/12.1Part1.387

S. Roush and F. Slack, The let-7 family of microRNAs, Trends in Cell Biology, vol.18, issue.10, pp.505-521, 2008.
DOI : 10.1016/j.tcb.2008.07.007

J. Lu, G. Getz, and E. Miska, MicroRNA expression profiles classify human cancers, Nature, vol.1, issue.7043, pp.834-842, 2005.
DOI : 10.1016/S1535-6108(02)00018-1

V. Sampson, N. Rong, and J. Han, MicroRNA Let-7a Down-regulates MYC and Reverts MYC-Induced Growth in Burkitt Lymphoma Cells, Cancer Research, vol.67, issue.20, pp.9762-70, 2007.
DOI : 10.1158/0008-5472.CAN-07-2462
URL : http://cancerres.aacrjournals.org/content/canres/67/20/9762.full.pdf

S. Shell, S. Park, and A. Radjabi, Let-7 expression defines two differentiation stages of cancer miR-99a/100~125b tricistrons regulate hematopoietic stem and progenitor cell homeostasis by shifting the balance between TGFbeta and Wnt signaling Genetic screen identifies microRNA cluster 99b/let-7e/125a as a regulator of primitive hematopoietic cells, Proceedings of the National Academy of Sciences of the United States of America Genes Dev Blood, vol.10428119, pp.11400-5858, 2007.

F. Wulczyn, L. Smirnova, and A. Rybak, microRNA during neural cell specification, The FASEB Journal, vol.21, issue.2, pp.415-441, 2007.
DOI : 10.1126/science.1065329

S. Viswanathan, G. Daley, and R. Gregory, Selective Blockade of MicroRNA Processing by Lin28, Science, vol.435, issue.7043, pp.97-100, 2008.
DOI : 10.1038/nature03702

S. Viswanathan, J. Powers, and W. Einhorn, Lin28 promotes transformation and is associated with advanced human malignancies, Nature Genetics, vol.77, issue.7, pp.843-851, 2009.
DOI : 10.1038/nature06866
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2757943/pdf

C. Feng, V. Neumeister, and W. Ma, Lin28 regulates HER2 and promotes malignancy through multiple mechanisms, Cell Cycle, vol.63, issue.13, pp.2486-94, 2012.
DOI : 10.1038/nbt0210-117
URL : http://www.tandfonline.com/doi/pdf/10.4161/cc.20893?needAccess=true

C. King, M. Cuatrecasas, A. Castells, A. Sepulveda, J. Lee et al., LIN28B Promotes Colon Cancer Progression and Metastasis, Cancer Research, vol.71, issue.12, pp.4260-4268, 2011.
DOI : 10.1158/0008-5472.CAN-10-4637
URL : http://cancerres.aacrjournals.org/content/canres/71/12/4260.full.pdf

Y. Guo, Y. Chen, and H. Ito, Identification and characterization of lin-28 homolog B (LIN28B) in human hepatocellular carcinoma, Gene, vol.384, pp.51-61, 2006.
DOI : 10.1016/j.gene.2006.07.011

L. Nguyen, D. Robinton, and M. Seligson, Lin28b Is Sufficient to Drive Liver Cancer and Necessary for Its Maintenance in Murine Models, Cancer Cell, vol.26, issue.2, pp.248-61, 2014.
DOI : 10.1016/j.ccr.2014.06.018

J. Molenaar, R. Domingo-fernandez, and M. Ebus, LIN28B induces neuroblastoma and enhances MYCN levels via let-7 suppression, Nature Genetics, vol.65, issue.11, pp.1199-206, 2012.
DOI : 10.1016/j.cell.2010.09.011

S. Diskin, M. Capasso, and R. Schnepp, Common variation at 6q16 within HACE1 and LIN28B influences susceptibility to neuroblastoma, Nature Genetics, vol.1, issue.10, pp.1126-1156, 2012.
DOI : 10.2307/2281868
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3459292/pdf

A. Urbach, A. Yermalovich, and J. Zhang, Lin28 sustains early renal progenitors and induces Wilms tumor, Genes & Development, vol.28, issue.9, pp.971-82, 2014.
DOI : 10.1101/gad.237149.113
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4018495/pdf

H. Tu, S. Schwitalla, and Z. Qian, LIN28 cooperates with WNT signaling to drive invasive intestinal and colorectal adenocarcinoma in mice and humans, Genes & Development, vol.29, issue.10, pp.1074-86, 2015.
DOI : 10.1101/gad.256693.114

I. Myeloma-working and G. , Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: a report of the International Myeloma Working Group, Br J Haematol, vol.121, pp.749-57, 2003.

O. Shalem, N. Sanjana, and E. Hartenian, Genome-Scale CRISPR-Cas9 Knockout Screening in Human Cells, Science, vol.500, issue.6166, pp.84-91, 2014.
DOI : 10.1038/nmeth.2598
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4089965/pdf

X. Leleu, X. Jia, and J. Runnels, The Akt pathway regulates survival and homing in Waldenstrom macroglobulinemia, Blood, vol.110, issue.13, pp.4417-4443, 2007.
DOI : 10.1182/blood-2007-05-092098

M. Tomayko and C. Reynolds, Determination of subcutaneous tumor size in athymic (nude) mice, Cancer Chemotherapy and Pharmacology, vol.45, issue.3, pp.148-54, 1989.
DOI : 10.1038/bjc.1985.57

N. Shyh-chang and G. Daley, Lin28: Primal Regulator of Growth and Metabolism in Stem Cells, Cell Stem Cell, vol.12, issue.4, pp.395-406, 2013.
DOI : 10.1016/j.stem.2013.03.005

L. Zhang, S. Volinia, and T. Bonome, Genomic and epigenetic alterations deregulate microRNA expression in human epithelial ovarian cancer, Proceedings of the National Academy of Sciences, vol.134, issue.2, pp.7004-7013, 2008.
DOI : 10.1242/dev.02726
URL : http://www.pnas.org/content/105/19/7004.full.pdf

K. Nagayama, T. Kohno, M. Sato, Y. Arai, J. Minna et al., Homozygous deletion scanning of the lung cancer genome at a 100-kb resolution, Genes, Chromosomes and Cancer, vol.22, issue.(Part 1), pp.1000-1010, 2007.
DOI : 10.1002/gcc.20485

H. Yamada, K. Yanagisawa, and S. Tokumaru, Detailed characterization of a homozygously deleted region corresponding to a candidate tumor suppressor locus at 21q11-21 in human lung cancer, Genes, Chromosomes and Cancer, vol.200, issue.9, pp.810-818, 2008.
DOI : 10.1002/gcc.20582

L. Lu, D. Katsaros, I. De-la-longrais, O. Sochirca, and H. Yu, Hypermethylation of let-7a-3 in Epithelial Ovarian Cancer Is Associated with Low Insulin-like Growth Factor-II Expression and Favorable Prognosis, Cancer Research, vol.67, issue.21, pp.10117-10139, 2007.
DOI : 10.1158/0008-5472.CAN-07-2544

L. Liang, C. Wong, and Q. Ying, MicroRNA-125b suppressesed human liver cancer cell proliferation and metastasis by directly targeting oncogene LIN28B2, Hepatology, vol.28, issue.5
DOI : 10.1002/hep.23904
URL : http://onlinelibrary.wiley.com/doi/10.1002/hep.23904/pdf

J. Wang, N. Cao, and M. Yuan, MicroRNA-125b/Lin28 Pathway Contributes to the Mesendodermal Fate Decision of Embryonic Stem Cells, Stem Cells and Development, vol.21, issue.9, pp.1524-1561, 2012.
DOI : 10.1089/scd.2011.0350

A. Rybak, H. Fuchs, and L. Smirnova, A feedback loop comprising lin-28 and let, p.7
DOI : 10.1038/ncb1759

S. Segalla, S. Pivetti, and K. Todoerti, The ribonuclease DIS3 promotes let, p.7
DOI : 10.1093/nar/gkv387
URL : https://academic.oup.com/nar/article-pdf/43/10/5182/17435101/gkv387.pdf

J. Lohr, P. Stojanov, and S. Carter, Widespread Genetic Heterogeneity in Multiple Myeloma: Implications for Targeted Therapy, Cancer Cell, vol.25, issue.1, pp.91-101, 2014.
DOI : 10.1016/j.ccr.2013.12.015

N. Bolli, H. Avet-loiseau, and D. Wedge, Heterogeneity of genomic evolution and mutational profiles in multiple myeloma, Nature Communications, vol.173, p.2997, 2014.
DOI : 10.1534/genetics.105.044677

W. Chng, A. Dispenzieri, and C. Chim, IMWG consensus on risk stratification in multiple myeloma, Leukemia, vol.8, issue.2, pp.269-77, 2014.
DOI : 10.1371/journal.pone.0066361

H. Avet-loiseau, B. Durie, and M. Cavo, Combining fluorescent in situ hybridization data with ISS staging improves risk assessment in myeloma: an International Myeloma Working Group collaborative project, Leukemia, vol.88, issue.3, pp.711-718, 2013.
DOI : 10.1200/JCO.2011.36.5726

C. Thery, L. Zitvogel, and S. Amigorena, Exosomes: composition, biogenesis and function, Nature Reviews Immunology, vol.267, issue.8, pp.569-79, 2002.
DOI : 10.1046/j.1432-1327.2000.01036.x

H. Peinado, M. Aleckovic, and S. Lavotshkin, Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET, Nature Medicine, vol.26, issue.6, pp.883-91, 2012.
DOI : 10.1093/jnci/djq153
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645291/pdf

A. Roccaro, A. Sacco, and P. Maiso, BM mesenchymal stromal cell???derived exosomes facilitate multiple myeloma progression, Journal of Clinical Investigation, vol.123, issue.4, pp.1542-55, 2013.
DOI : 10.1172/JCI66517DS1
URL : http://www.jci.org/articles/view/66517/files/pdf

S. Melo, H. Sugimoto, O. Connell, and J. , Cancer Exosomes Perform Cell-Independent MicroRNA Biogenesis and Promote Tumorigenesis, Cancer Cell, vol.26, issue.5, pp.707-728, 2014.
DOI : 10.1016/j.ccell.2014.09.005
URL : https://doi.org/10.1016/j.ccell.2014.09.005

J. Krol, I. Loedige, and W. Filipowicz, The widespread regulation of microRNA biogenesis, function and decay, Nature Reviews Genetics, vol.36, issue.9, pp.597-610, 2010.
DOI : 10.1038/nrg2843

F. Pichiorri, S. Suh, and M. Ladetto, MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis, Proceedings of the National Academy of Sciences, vol.101, issue.26, pp.12885-90, 2008.
DOI : 10.1073/pnas.0403293101
URL : http://www.pnas.org/content/105/35/12885.full.pdf

N. Gutierrez, M. 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.629-666, 2010.
DOI : 10.1038/sj.leu.2404520

G. Calin, M. Ferracin, and A. Cimmino, A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia, New England Journal of Medicine, vol.353, issue.17, pp.1793-801, 2005.
DOI : 10.1056/NEJMoa050995

N. Yanaihara, N. Caplen, and E. Bowman, Unique microRNA molecular profiles in lung cancer diagnosis and prognosis, Cancer Cell, vol.9, issue.3, pp.189-98, 2006.
DOI : 10.1016/j.ccr.2006.01.025
URL : https://doi.org/10.1016/j.ccr.2006.01.025

S. Yu, H. Chen, and G. Chang, MicroRNA Signature Predicts Survival and Relapse in Lung Cancer, Cancer Cell, vol.13, issue.1, pp.48-57, 2008.
DOI : 10.1016/j.ccr.2007.12.008
URL : https://doi.org/10.1016/j.ccr.2007.12.008

T. Ueda, S. Volinia, and H. Okumura, Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis, The Lancet Oncology, vol.11, issue.2
DOI : 10.1016/S1470-2045(09)70343-2

N. Liu, N. Chen, and R. Cui, Prognostic value of a microRNA signature in nasopharyngeal carcinoma: a microRNA expression analysis, The Lancet Oncology, vol.13, issue.6, pp.633-674, 2012.
DOI : 10.1016/S1470-2045(12)70102-X

B. Durie, J. Harousseau, and J. Miguel, International uniform response criteria for multiple myeloma, Leukemia, vol.27, issue.9, pp.1467-73, 2006.
DOI : 10.1038/sj.bmt.1703035
URL : http://www.nature.com/leu/journal/v20/n9/pdf/2404284a.pdf

D. Taylor, W. Zacharias, and C. Gercel-taylor, Exosome Isolation for Proteomic Analyses and RNA Profiling, Methods Mol Biol, vol.728, pp.235-281, 2011.
DOI : 10.1007/978-1-61779-068-3_15

M. Kodani, G. Yang, and L. Conklin, Application of TaqMan Low-Density Arrays for Simultaneous Detection of Multiple Respiratory Pathogens, Journal of Clinical Microbiology, vol.49, issue.6, pp.2175-82, 2011.
DOI : 10.1128/JCM.02270-10

D. Haene, B. Mestdagh, P. Hellemans, J. Vandesompele, and J. , miRNA expression profiling: from reference genes to global mean normalization, Methods Mol Biol, vol.822, pp.261-72, 2012.

H. Schwarzenbach, N. Nishida, G. Calin, and K. Pantel, Clinical relevance of circulating cell-free microRNAs in cancer, Nature Reviews Clinical Oncology, vol.20, issue.3, pp.145-56, 2014.
DOI : 10.1245/s10434-013-3093-4

L. Kubiczkova, F. Kryukov, and O. Slaby, Circulating serum microRNAs as novel diagnostic and prognostic biomarkers for multiple myeloma and monoclonal gammopathy of undetermined significance, Haematologica, vol.99, issue.3, pp.511-519, 2014.
DOI : 10.3324/haematol.2013.093500

M. Hao, M. Zang, and E. Wendlandt, Low serum miR-19a expression as a novel poor prognostic indicator in multiple myeloma, International Journal of Cancer, vol.434, issue.8, pp.1835-1879, 2015.
DOI : 10.1016/j.bbrc.2013.04.010

A. Rocci, C. Hofmeister, and S. Geyer, Circulating miRNA markers show promise as new prognosticators for multiple myeloma, Leukemia, vol.109, issue.9, pp.1922-1928, 2014.
DOI : 10.1073/pnas.1209414109
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155011/pdf

X. Huang, T. Yuan, and M. Liang, Exosomal miR-1290 and miR-375 as Prognostic Markers in Castration-resistant Prostate Cancer, European Urology, vol.67, issue.1, pp.33-41, 2015.
DOI : 10.1016/j.eururo.2014.07.035

S. Melo, L. Luecke, and C. Kahlert, Glypican-1 identifies cancer exosomes and detects early pancreatic cancer, Nature, vol.44, issue.7559, pp.177-82, 2015.
DOI : 10.2307/2531595
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4825698/pdf

M. Xiang, Y. Zeng, and R. Yang, U6 is not a suitable endogenous control for the quantification of circulating microRNAs, Biochemical and Biophysical Research Communications, vol.454, issue.1, pp.210-214, 2014.
DOI : 10.1016/j.bbrc.2014.10.064

P. Mestdagh, P. Van-vlierberghe, D. Weer, and A. , A novel and universal method for microRNA RT-qPCR data normalization, Genome Biology, vol.10, issue.6, p.64, 2009.
DOI : 10.1186/gb-2009-10-6-r64
URL : https://genomebiology.biomedcentral.com/track/pdf/10.1186/gb-2009-10-6-r64?site=genomebiology.biomedcentral.com

W. Cui, J. Ma, Y. Wang, and S. Biswal, Plasma miRNA as Biomarkers for Assessment of Total-Body Radiation Exposure Dosimetry, PLoS ONE, vol.94, issue.8, p.22988, 2011.
DOI : 10.1371/journal.pone.0022988.s001

S. Manier, J. Powers, and A. Sacco, The LIN28B/let-7 axis is a novel therapeutic pathway in multiple myeloma, Leukemia, vol.5, issue.4, 2016.
DOI : 10.1038/ncomms3997

A. Jacobsen, J. Silber, G. Harinath, J. Huse, N. Schultz et al., Analysis of microRNA-target interactions across diverse cancer types, Nature Structural & Molecular Biology, vol.2, issue.11, pp.1325-1357, 2013.
DOI : 10.1074/jbc.M707224200

J. Mendell, miRiad Roles for the miR-17-92 Cluster in Development and Disease, Cell, vol.133, issue.2, pp.217-239, 2008.
DOI : 10.1016/j.cell.2008.04.001

R. Krutilina, W. Sun, and A. Sethuraman, MicroRNA-18a inhibits hypoxia-inducible factor 1?? activity and lung metastasis in basal breast cancers, Breast Cancer Research, vol.4, issue.4, p.78, 2014.
DOI : 10.1016/S1535-6108(03)00194-6

Y. Teng, J. Mu, and X. Hu, Grapefruit-derived nanovectors deliver miR-18a for treatment of liver metastasis of colon cancer by induction of M1 macrophages, Oncotarget, vol.7, issue.18
DOI : 10.18632/oncotarget.8361

M. Truitt and D. Ruggero, New frontiers in translational control of the cancer genome, Nature Reviews Cancer, vol.6, issue.5, pp.288-304, 2016.
DOI : 10.1038/nmeth.3478

M. Truitt, C. Conn, and Z. Shi, Differential Requirements for eIF4E Dose in Normal Development and Cancer, Cell, vol.162, issue.1, pp.59-71, 2015.
DOI : 10.1016/j.cell.2015.05.049

M. Bhat, N. Robichaud, L. Hulea, N. Sonenberg, J. Pelletier et al., Targeting the translation machinery in cancer, Nature Reviews Drug Discovery, vol.269, issue.4, pp.261-78, 2015.
DOI : 10.2337/dc14-0500

C. Vogel and E. Marcotte, Insights into the regulation of protein abundance from proteomic and transcriptomic analyses, Nature Reviews Genetics, vol.285, issue.4, pp.227-259, 2012.
DOI : 10.1074/jbc.R109.077883

L. Brown, C. Cheng, K. Wei, and W. , Discovery of new antimalarial chemotypes through chemical methodology and library development, Proceedings of the National Academy of Sciences, vol.58, issue.3, pp.6775-80, 2011.
DOI : 10.1002/hlca.19750580312

C. Rodrigo, R. Cencic, S. Roche, J. Pelletier, and J. Porco, Synthesis of Rocaglamide Hydroxamates and Related Compounds as Eukaryotic Translation Inhibitors: Synthetic and Biological Studies, Journal of Medicinal Chemistry, vol.55, issue.1, pp.558-62, 2012.
DOI : 10.1021/jm201263k

M. Bordeleau, F. Robert, and B. Gerard, Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model, Journal of Clinical Investigation, vol.118, pp.2651-60, 2008.
DOI : 10.1172/JCI34753DS1

J. Chu, R. Cencic, W. Wang, J. Porco, J. Pelletier et al., Translation Inhibition by Rocaglates Is Independent of eIF4E Phosphorylation Status, Molecular Cancer Therapeutics, vol.15, issue.1, pp.136-177, 2016.
DOI : 10.1158/1535-7163.MCT-15-0409

A. Subramanian, P. Tamayo, and V. Mootha, Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles, Proceedings of the National Academy of Sciences, vol.19, issue.18, pp.15545-50, 2005.
DOI : 10.1093/bioinformatics/btg363
URL : http://www.pnas.org/content/102/43/15545.full.pdf

S. Santagata, M. Mendillo, and Y. Tang, Tight Coordination of Protein Translation and HSF1 Activation Supports the Anabolic Malignant State, Science, vol.22, issue.24, p.1238303, 2013.
DOI : 10.1101/gad.1741408

M. Mendillo, S. Santagata, and M. Koeva, HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers, Cell, vol.150, issue.3, pp.549-62, 2012.
DOI : 10.1016/j.cell.2012.06.031
URL : https://doi.org/10.1016/j.cell.2012.06.031

L. Agnelli, S. Bicciato, and M. Mattioli, and Negative for 14q32 Translocations, Journal of Clinical Oncology, vol.23, issue.29, pp.7296-306, 2005.
DOI : 10.1200/JCO.2005.01.3870

F. Zhan, Y. Huang, and S. Colla, The molecular classification of multiple myeloma, Blood, vol.108, issue.6, pp.2020-2028, 2006.
DOI : 10.1182/blood-2005-11-013458

G. Mulligan, C. Mitsiades, and B. Bryant, Gene expression profiling and correlation with outcome in clinical trials of the proteasome inhibitor bortezomib, Blood, vol.109, issue.8, pp.3177-88, 2007.
DOI : 10.1182/blood-2006-09-044974

E. Huttlin, M. Jedrychowski, and J. Elias, A Tissue-Specific Atlas of Mouse Protein Phosphorylation and Expression, Cell, vol.143, issue.7, pp.1174-89, 2010.
DOI : 10.1016/j.cell.2010.12.001

M. Wade, Y. Li, and G. Wahl, MDM2, MDMX and p53 in oncogenesis and cancer therapy, Nature Reviews Cancer, vol.107, issue.2, pp.83-96, 2013.
DOI : 10.1073/pnas.1008930107

R. Beroukhim, C. Mermel, and D. Porter, The landscape of somatic copy-number alteration across human cancers, Nature, vol.21, issue.7283, pp.899-905, 2010.
DOI : 10.4161/cc.6.6.4035

E. Hurt, A. Wiestner, and A. Rosenwald, Overexpression of c-maf is a frequent oncogenic event in multiple myeloma that promotes proliferation and pathological interactions with bone marrow stroma, Cancer Cell, vol.5, issue.2, pp.191-200, 2004.
DOI : 10.1016/S1535-6108(04)00019-4

N. Sonenberg and A. Hinnebusch, Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets, Cell, vol.136, issue.4, pp.731-776, 2009.
DOI : 10.1016/j.cell.2009.01.042

M. Kozak, Influences of mRNA secondary structure on initiation by eukaryotic ribosomes., Proceedings of the National Academy of Sciences, vol.83, issue.9, pp.2850-2854, 1986.
DOI : 10.1073/pnas.83.9.2850

J. Pelletier and N. Sonenberg, Insertion mutagenesis to increase secondary structure within the 5??? noncoding region of a eukaryotic mRNA reduces translational efficiency, Cell, vol.40, issue.3, pp.515-541, 1985.
DOI : 10.1016/0092-8674(85)90200-4

A. Koromilas, A. Lazaris-karatzas, and N. Sonenberg, mRNAs containing extensive secondary structure in their 5' non-coding region translate efficiently in cells overexpressing initiation factor eIF-4E, EMBO J, vol.11, pp.4153-4161, 1992.

K. Feoktistova, E. Tuvshintogs, A. Do, and C. Fraser, Human eIF4E promotes mRNA restructuring by stimulating eIF4A helicase activity, Proceedings of the National Academy of Sciences, vol.310, issue.5753, pp.13339-13383, 2013.
DOI : 10.1126/science.1118977
URL : http://www.pnas.org/content/110/33/13339.full.pdf

A. Wolfe, K. Singh, and Y. Zhong, RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer, Nature, vol.18, issue.7516, pp.65-70, 2014.
DOI : 10.1261/rna.033209.112
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492470/pdf

S. Iwasaki, S. Floor, and N. Ingolia, Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor, Nature, vol.18, issue.7608, pp.558-61, 2016.
DOI : 10.1261/rna.033209.112
URL : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946961/pdf

N. Lajkiewicz, S. Roche, B. Gerard, J. Porco, and J. , Enantioselective photocycloaddition of 3-hydroxyflavones: total syntheses and absolute configuration