F. R. Appelbaum, H. Gundacker, D. R. Head, M. L. Slovak, C. L. Willman et al., Age and acute myeloid leukemia, Blood, vol.107, pp.3481-3485, 2006.

A. Burnett, M. Wetzler, and B. Lowenberg, Therapeutic advances in acute myeloid leukemia, J Clin Oncol, vol.29, pp.487-494, 2011.

A. H. Goldstone, A. K. Burnett, K. Wheatley, A. G. Smith, R. M. Hutchinson et al., Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial, Blood, vol.98, pp.1302-1311, 2001.

A. K. Burnett, D. Milligan, A. G. Prentice, A. H. Goldstone, M. F. Mcmullin et al., Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel, A References, vol.1, issue.4, pp.424-447, 2017.

P. Bories, S. Bertoli, and E. Bérard, Intensive chemotherapy, azacitidine, or supportive care in older acute myeloid leukemia patients: an analysis from a regional healthcare network, Am J Hematol, vol.89, issue.12, pp.244-252, 2014.

H. D. Klepin, A. V. Rao, and T. S. Pardee, Acute myeloid leukemia and myelodysplastic syndromes in older adults, J Clin Oncol, vol.32, issue.24, pp.2541-2552, 2014.

C. Tsai, H. Hou, and J. Tang, Genetic alterations and their clinical implications in older patients with acute myeloid leukemia, Leukemia, vol.30, issue.7, pp.1485-1492, 2016.

U. Krug, C. Röllig, and A. Koschmieder, Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a webbased application for prediction of outcomes, Lancet, vol.376, issue.9757, pp.2000-2008, 2010.

H. D. Klepin, A. M. Geiger, and J. A. Tooze, Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia, Blood, vol.121, issue.21, pp.4287-4294, 2013.

F. R. Loberiza, A. C. Cannon, A. J. Cannon, and P. J. Bierman, Insights on practice variations in the management of lymphoma and leukemia, Leuk Lymphoma, vol.55, issue.11, pp.2449-2456, 2014.

H. Dombret, J. F. Seymour, and A. Butrym, International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts, Blood, vol.126, issue.3, pp.291-299, 2015.

H. M. Kantarjian, X. G. Thomas, and A. Dmoszynska, Multicenter, randomized, openlabel, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia, J Clin Oncol, vol.30, issue.21, pp.2670-2677, 2012.

A. K. Burnett, D. Milligan, and A. Goldstone, The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial, Br J Haematol, vol.145, issue.3, pp.318-332, 2009.

A. K. Burnett, D. Milligan, and A. G. Prentice, A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment, Cancer, vol.109, issue.6, pp.1114-1124, 2007.

S. J. Lee, S. Joffe, and A. S. Artz, Individual physician practice variation in hematopoietic cell transplantation, J Clin Oncol, vol.26, issue.13, pp.2162-2170, 2008.

S. J. Lee, C. C. Astigarraga, and M. Eapen, Variation in supportive care practices in hematopoietic cell transplantation, Biol Blood Marrow Transplant, vol.14, issue.11, pp.1231-1238, 2008.

T. Dhawale, L. M. Steuten, and H. J. Deeg, Uncertainty of Physicians and Patients in Medical Decision Making, Biol Blood Marrow Transplant, vol.23, issue.6, pp.865-869, 2017.

D. J. Hunter, Uncertainty in the Era of Precision Medicine, N Engl J Med, vol.375, issue.8, pp.711-713, 2016.

A. L. Simpkin and R. M. Schwartzstein, Tolerating Uncertainty -The Next Medical Revolution?, N Engl J Med, vol.375, issue.18, pp.1713-1715, 2016.

A. Michel-lepage, B. Ventelou, A. Nebout, P. Verger, and C. Pulcini, Cross-sectional survey: risk-averse French GPs use more rapid-antigen diagnostic tests in tonsillitis in children, BMJ Open, vol.3, issue.10, p.3540, 2013.
URL : https://hal.archives-ouvertes.fr/hal-01500874

S. Massin, B. Ventelou, A. Nebout, P. Verger, and C. Pulcini, Cross-sectional survey: riskaverse French general practitioners are more favorable toward influenza vaccination, Vaccine, vol.33, issue.5, pp.610-614, 2015.
URL : https://hal.archives-ouvertes.fr/hal-01241634

J. Von-neumann and O. Morgenstern, Theory of Games and Economic Behavior, vol.625, 1947.

C. Starmer, Developments in Non-expected Utility Theory: The Hunt for a Descriptive Theory of Choice under Risk, J Econ Lit, vol.38, issue.2, pp.332-382, 2000.

D. Kahneman and A. Tversky, Prospect Theory: An Analysis of Decision under Risk, Econometrica, vol.47, issue.2, pp.263-291, 1979.

M. Allais, Le Comportement de l'Homme Rationnel devant le Risque: Critique des Postulats et Axiomes de l'Ecole Americaine, Econometrica, vol.21, issue.4, pp.503-546, 1953.

P. P. Wakker, Prospect Theory: For Risk and Ambiguity, vol.518, 2010.

A. Lipitz-snyderman, C. S. Sima, and C. L. Atoria, Physician-Driven Variation in Nonrecommended Services Among Older Adults Diagnosed With Cancer, JAMA Intern Med, vol.176, issue.10, pp.1541-1548, 2016.

J. J. Sikkens, M. A. Van-agtmael, and E. Peters, Behavioral Approach to Appropriate Antimicrobial Prescribing in Hospitals: The Dutch Unique Method for Antimicrobial Stewardship (DUMAS) Participatory Intervention Study, JAMA Intern Med, vol.177, issue.8, pp.1130-1138, 2017.

J. W. Peabody, J. Luck, P. Glassman, T. R. Dresselhaus, and M. Lee, Comparison of vignettes, standardized patients, and chart abstraction: a prospective validation study of 3 methods for measuring quality, JAMA, vol.283, issue.13, pp.1715-1722, 2000.

T. Dohmen, A. Falk, D. Huffman, U. Sunde, J. Schupp et al., Individual risk attitudes: Measurement, determinants, and behavioral consequences, J Eur Econ Assoc, vol.9, issue.3, pp.522-550, 2011.

S. Z. Selim and M. A. Ismail, K-means-type algorithms: a generalized convergence theorem and characterization of local optimality, IEEE Trans Pattern Anal Mach Intell, vol.6, issue.1, pp.81-87, 1984.

S. Y. Kristinsson, A. R. Derolf, G. Edgren, P. W. Dickman, and M. Björkholm, Socioeconomic differences in patient survival are increasing for acute myeloid leukemia and multiple myeloma in sweden, J Clin Oncol, vol.27, issue.12, pp.2073-2080, 2009.

U. M. Borate, S. Mineishi, and L. J. Costa, Nonbiological factors affecting survival in younger patients with acute myeloid leukemia, Cancer, vol.121, issue.21, pp.3877-3884, 2015.

R. Luo, S. H. Giordano, D. D. Zhang, J. Freeman, and J. S. Goodwin, The role of the surgeon in whether patients with lymph node-positive colon cancer see a medical oncologist, Cancer, vol.109, issue.5, pp.975-982, 2007.

S. Giri, R. Pathak, M. R. Aryal, P. Karmacharya, V. R. Bhatt et al., Impact of hospital volume on outcomes of patients undergoing chemotherapy for acute myeloid leukemia: a matched cohort study, J Clin Oncol, vol.125, issue.21, pp.598-604, 2015.

B. E. Hillner, T. J. Smith, and C. E. Desch, Hospital and physician volume or specialization and outcomes in cancer treatment: importance in quality of cancer care, J Clin Oncol, vol.18, issue.11, pp.2327-2340, 2000.

A. A. Verma, F. Razak, and A. S. Detsky, Understanding choice: why physicians should learn prospect theory, JAMA, vol.311, issue.6, pp.571-572, 2014.

P. Han, B. B. Reeve, R. P. Moser, and W. Klein, Aversion to ambiguity regarding medical tests and treatments: measurement, prevalence, and relationship to sociodemographic factors, J Health Commun, vol.14, issue.6, pp.556-572, 2009.

A. Nebout and D. Dubois, When Allais meets Ulysses: Dynamic axioms and the common ratio effect, J Risk Uncertain, vol.48, issue.1, pp.19-49, 2014.
URL : https://hal.archives-ouvertes.fr/hal-01065114

S. T. Trautmann, G. Van-de-kuilen, . Ltd, . Chichester, G. Uk:-g.-keren et al., Comparing GPs' risk attitudes for their own health and for their patients' : a troubling discrepancy?, The Wiley Blackwell Handbook of Judgment and Decision Making, vol.18, pp.1061-1073, 2018.

R. Croson and U. Gneezy, Gender Differences in Preferences, J Econ Lit, vol.47, issue.2, pp.448-474, 2009.

M. Gattellari, K. J. Voigt, P. N. Butow, and M. Tattersall, When the treatment goal is not cure: are cancer patients equipped to make informed decisions?, J Clin Oncol, vol.20, issue.2, pp.503-513, 2002.

P. Han, W. Klein, T. Lehman, B. Killam, H. Massett et al., Communication of uncertainty regarding individualized cancer risk estimates: effects and influential factors. Med Decis Mak Int, J Soc Med Decis Mak, vol.31, issue.2, pp.354-366, 2011.

A. G. Dinmohamed, O. Visser, and Y. Van-norden, Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, Leukemia, vol.30, issue.1, pp.24-31, 1989.

B. C. Medeiros, A. T. Fathi, C. D. Dinardo, D. A. Pollyea, S. M. Chan et al., Isocitrate dehydrogenase mutations in myeloid malignancies, Leukemia, vol.31, issue.2, pp.272-281, 2017.

J. S. Welch, A. A. Petti, and C. A. Miller, TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes, N Engl J Med, vol.375, issue.21, pp.2023-2036, 2016.

M. Gerstung, E. Papaemmanuil, and I. Martincorena, Precision oncology for acute myeloid leukemia using a knowledge bank approach, Nat Genet, vol.49, issue.3, pp.332-340, 2017.

M. L. Sorror, B. E. Storer, and A. T. Fathi, Development and Validation of a Novel Acute Myeloid Leukemia-Composite Model to Estimate Risks of Mortality, JAMA Oncol, vol.3, issue.12, pp.1675-1682, 2017.

S. Bertoli, S. Tavitian, A. Huynh, C. Borel, S. Guenounou et al., Improved outcome for AML patients over the years 2000-2014, Blood Cancer J, vol.7, p.635, 2017.

A. R. Derolf, S. Y. Kristinsson, T. Andersson, O. Landgren, P. W. Dickman et al., Improved patient survival for acute myeloid leukemia: a population-based study of 9729 patients diagnosed in Sweden between, Blood, vol.113, pp.3666-3672, 1973.

H. Döhner, E. Estey, D. Grimwade, S. Amadori, F. R. Appelbaum et al., Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel, Blood, vol.129, pp.424-447, 2017.

P. Bories, S. Bertoli, E. Bérard, J. Laurent, E. Duchayne et al., Intensive chemotherapy, azacitidine, or supportive care in older acute myeloid leukemia patients: an analysis from a regional healthcare network, Am J Hematol, vol.89, pp.244-252, 2014.

P. Bories, S. Lamy, C. Simand, S. Bertoli, C. Delpierre et al., Physician uncertainty aversion impacts medical decision making for older patients with acute myeloid leukemia: results of a national survey, Haematologica, 2018.
URL : https://hal.archives-ouvertes.fr/hal-01905870

G. Juliusson, A. Swedish, and . Group, Most 70-to 79-year-old patients with acute myeloid leukemia do benefit from intensive treatment, Blood, vol.117, pp.3473-3474, 2011.

H. Kantarjian, F. Ravandi, S. O'brien, J. Cortes, S. Faderl et al., Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia, Blood, vol.116, pp.4422-4429, 2010.

H. Dombret, J. F. Seymour, A. Butrym, A. Wierzbowska, D. Selleslag et al., International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts, Blood, vol.126, pp.291-299, 2015.

M. Lübbert, B. H. Rüter, C. R. Schmoor, C. Schmid, M. Germing et al., A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy, Haematologica, vol.97, pp.393-401, 2012.

F. Ravandi, J. Issa, G. Garcia-manero, O. 'brien, S. Pierce et al., Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities, Cancer, vol.115, pp.5746-5751, 2009.

E. K. Ritchie, E. J. Feldman, P. J. Christos, S. D. Rohan, C. B. Lagassa et al., Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia, Leuk Lymphoma, vol.54, pp.2003-2007, 2013.

D. Bowen, M. J. Groves, A. K. Burnett, Y. Patel, C. Allen et al., TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis, Leukemia, vol.23, pp.203-206, 2009.

C. Haferlach, F. Dicker, H. Herholz, S. Schnittger, W. Kern et al., Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype, Leukemia, vol.22, pp.1539-1541, 2008.

F. G. Rücker, R. F. Schlenk, L. Bullinger, S. Kayser, V. Teleanu et al., TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome, Blood, vol.119, pp.2114-2121, 2012.

T. M. Kadia, P. Jain, F. Ravandi, G. Garcia-manero, M. Andreef et al., TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes. Cancer, 2016.

J. M. Middeke, S. Herold, E. Rücker-braun, W. E. Berdel, M. Stelljes et al., TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation, Br J Haematol, vol.172, pp.914-922, 2016.

S. O. Ciurea, A. Chilkulwar, R. M. Saliba, J. Chen, G. Rondon et al., Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations, Blood, vol.131, pp.2989-2992, 2018.

R. Bejar, K. E. Stevenson, B. Caughey, R. C. Lindsley, B. G. Mar et al., Somatic mutations predict poor outcome in patients with myelodysplastic syndrome after hematopoietic stem-cell transplantation, J Clin Oncol, vol.32, pp.2691-2698, 2014.

R. Bejar, A. Lord, K. Stevenson, M. Bar-natan, A. Pérez-ladaga et al., TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients, Blood, vol.124, pp.2705-2712, 2014.

M. Nieto, E. Samper, M. F. Fraga, G. De-buitrago, G. Esteller et al., The absence of p53 is critical for the induction of apoptosis by 5-aza-2'-deoxycytidine, Oncogene, vol.23, pp.735-743, 2004.

L. Yi, Y. Sun, and A. Levine, Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells, Oncotarget, vol.5, pp.8924-8936, 2014.

B. C. Mckay, C. Becerril, and M. Ljungman, P53 plays a protective role against UV-and cisplatininduced apoptosis in transcription-coupled repair proficient fibroblasts, Oncogene, vol.20, pp.6805-6808, 2001.

A. V. Gudkov and E. A. Komarova, The role of p53 in determining sensitivity to radiotherapy, Nat Rev Cancer, vol.3, pp.117-129, 2003.

J. S. Welch, A. A. Petti, C. A. Miller, C. C. Fronick, M. O'laughlin et al., TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes, N Engl J Med, vol.375, pp.2023-2036, 2016.

K. Sabapathy and D. P. Lane, Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others, Nat Rev Clin Oncol, vol.15, pp.13-30, 2018.

M. L. Poeta, J. Manola, M. A. Goldwasser, A. Forastiere, N. Benoit et al., TP53 mutations and survival in squamous-cell carcinoma of the head and neck, N Engl J Med, vol.357, pp.2552-2561, 2007.

D. M. Neskey, A. A. Osman, T. J. Ow, P. Katsonis, T. Mcdonald et al., Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer, Cancer Res, vol.75, pp.1527-1536, 2015.

K. H. Young, D. D. Weisenburger, B. J. Dave, L. Smith, W. Sanger et al., Mutations in the DNAbinding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma, Blood, vol.110, pp.4396-4405, 2007.

P. Dumas, S. Bertoli, E. Bérard, C. Médiavilla, Y. E. Tavitian et al., Azacitidine or intensive chemotherapy for older patients with secondary or therapy-related acute myeloid leukemia, Oncotarget, vol.8, pp.79126-79136, 2017.

D. Grimwade, R. K. Hills, A. V. Moorman, H. Walker, S. Chatters et al., Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials, Blood, vol.116, pp.354-365, 2010.

L. Bouaoun, D. Sonkin, M. Ardin, M. Hollstein, G. Byrnes et al., TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data, vol.37, pp.865-876, 2016.

A. Willis, E. J. Jung, T. Wakefield, and X. Chen, Mutant p53 exerts a dominant negative effect by preventing wild-type p53 from binding to the promoter of its target genes, Oncogene, vol.23, pp.2330-2338, 2004.

Y. S. Chun, G. Passot, S. Yamashita, M. Nusrat, P. Katsonis et al., Deleterious Effect of RAS and Evolutionary High-risk TP53 Double Mutation in Colorectal Liver Metastases, Ann Surg, 2017.

E. Kotler, O. Shani, G. Goldfeld, M. Lotan-pompan, O. Tarcic et al., A Systematic, p.53

, Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation, Mol Cell, vol.71, pp.178-190, 2018.

B. D. Cheson, P. L. Greenberg, J. M. Bennett, B. Lowenberg, P. W. Wijermans et al., Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia, Blood, vol.108, pp.419-425, 2006.

V. V. Prassek, M. Rothenberg-thurley, M. C. Sauerland, T. Herold, H. Janke et al., Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged ? 75 years, Haematologica, 2018.

A. Stengel, W. Kern, T. Haferlach, M. Meggendorfer, A. Fasan et al., The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases, Leukemia, vol.31, pp.705-711, 2017.

C. Tsai, H. Hou, J. Tang, C. Liu, C. Lin et al., Genetic alterations and their clinical implications in older patients with acute myeloid leukemia, Leukemia, vol.30, pp.1485-1492, 2016.

W. Blum, R. Garzon, R. B. Klisovic, S. Schwind, A. Walker et al., Clinical response and miR29b predictive significance in older AML patients treated with a 10-day schedule of decitabine, Proc Natl Acad Sci, vol.107, pp.7473-7478, 2010.

C. Bally, L. Adès, A. Renneville, M. Sebert, V. Eclache et al., Prognostic value of TP53 gene mutations in myelodysplastic syndromes and acute myeloid leukemia treated with azacitidine, Leuk Res, vol.38, pp.751-755, 2014.

M. K. Lee, W. W. Teoh, B. H. Phang, W. M. Tong, Z. Q. Wang et al., Cell-type, dose, and mutationtype specificity dictate mutant p53 functions in vivo, Cancer Cell, vol.22, pp.751-764, 2012.

G. Blandino, A. J. Levine, and M. Oren, Mutant p53 gain of function: differential effects of different p53 mutants on resistance of cultured cells to chemotherapy, Oncogene, vol.18, pp.477-485, 1999.

V. Bykov and K. G. Wiman, Mutant p53 reactivation by small molecules makes its way to the clinic, FEBS Lett, vol.588, pp.2622-2627, 2014.

M. Andreeff, K. R. Kelly, K. Yee, S. Assouline, R. Strair et al., Results of the Phase I Trial of RG7112, a Small-Molecule MDM2 Antagonist in Leukemia, Clin Cancer Res, vol.22, pp.868-876, 2016.

M. Prokocimer, A. Molchadsky, and V. Rotter, Dysfunctional diversity of p53 proteins in adult acute myeloid leukemia: projections on diagnostic workup and therapy, Blood, vol.130, pp.699-712, 2017.

H. Döhner, E. Estey, and D. Grimwade, Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel, Blood, vol.129, issue.4, pp.424-447, 2017.

P. Fenaux, G. J. Mufti, and E. Hellström-lindberg, Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia, J Clin Oncol, vol.28, issue.4, pp.562-569, 2010.

M. Rius, C. Stresemann, and D. Keller, Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation, Mol Cancer Ther, vol.8, issue.1, pp.225-231, 2009.

A. Valencia, E. Masala, and A. Rossi, Expression of nucleoside-metabolizing enzymes in myelodysplastic syndromes and modulation of response to azacitidine, Leukemia, vol.28, issue.3, pp.621-628, 2014.

R. Z. Mahfouz, A. Jankowska, and Q. Ebrahem, Increased CDA expression/activity in males contributes to decreased cytidine analog half-life and likely contributes to worse outcomes with 5-azacytidine or decitabine therapy, Clin Cancer Res, vol.19, issue.4, pp.938-948, 2013.

P. Fenaux, G. J. Mufti, and E. Hellstrom-lindberg, Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study, Lancet Oncol, vol.10, issue.3, pp.223-232, 2009.

R. Itzykson, O. Kosmider, and T. Cluzeau, Impact of TET2 mutations on response rate to azacitidine in myelodysplastic syndromes and low blast count acute myeloid leukemias, Leukemia, vol.25, issue.7, pp.1147-1152, 2011.

A. Emadi, R. Faramand, and B. Carter-cooper, Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia, Am J Hematol, vol.90, issue.5, pp.77-79, 2015.

K. H. Metzeler, A. Walker, and S. Geyer, DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia, Leukemia, vol.26, issue.5, pp.1106-1107, 2012.

C. D. Dinardo, K. P. Patel, and G. Garcia-manero, Lack of association of IDH1, IDH2 and DNMT3A mutations with outcome in older patients with acute myeloid leukemia treated with hypomethylating agents, Leuk Lymphoma, vol.55, issue.8, pp.1925-1929, 2014.

A. Kuendgen, C. Müller-thomas, and M. Lauseker, Efficacy of azacitidine is independent of molecular and clinical characteristics -an analysis of 128 patients with myelodysplastic syndromes or acute myeloid leukemia and a review of the literature, Oncotarget, vol.9, issue.45, pp.27882-27894, 2018.

L. Tang, A. Dolnik, and K. J. Macbeth, Impact of Gene Mutations on Overall Survival in Older Patients with Acute Myeloid Leukemia (AML) Treated with Azacitidine (AZA) or Conventional Care Regimens (CCR), Blood, vol.128, issue.22, p.2859, 2016.

J. S. Welch, A. A. Petti, and C. A. Miller, TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes, N Engl J Med, vol.375, issue.21, pp.2023-2036, 2016.

J. M. Klco, D. H. Spencer, and T. L. Lamprecht, Genomic impact of transient low-dose decitabine treatment on primary AML cells, Blood, vol.121, issue.9, pp.1633-1643, 2013.

T. E. Fandy, J. G. Herman, and P. Kerns, 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, issue.13, pp.2764-2773, 2009.

L. Shen, H. Kantarjian, and Y. Guo, DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes, J Clin Oncol, vol.28, issue.4, pp.605-613, 2010.

M. Tobiasson, H. Abdulkadir, and A. Lennartsson, Comprehensive mapping of the effects of azacitidine on DNA methylation, repressive/permissive histone marks and gene expression in primary cells from patients with MDS and MDS-related disease, Oncotarget, vol.8, issue.17, pp.28812-28825, 2017.

M. Grövdal, M. Karimi, and M. Tobiasson, Azacitidine induces profound genome-wide hypomethylation in primary myelodysplastic bone marrow cultures but may also reduce histone acetylation, Leukemia, vol.28, issue.2, pp.411-413, 2014.

B. D. Cheson, P. L. Greenberg, and J. M. Bennett, Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia, Blood, vol.108, issue.2, pp.419-425, 2006.

H. Zou and T. Hastie, Regularization and variable selection via the elastic net, Journal of the Royal Statistical Society: Series B (Statistical Methodology), vol.67, issue.2, pp.301-320, 2005.

S. Bertoli, S. Tavitian, and A. Huynh, Improved outcome for AML patients over the years 2000-2014, Blood Cancer J, vol.7, issue.12, p.635, 2017.

P. Dumas, S. Bertoli, and E. Bérard, Azacitidine or intensive chemotherapy for older patients with secondary or therapy-related acute myeloid leukemia, Oncotarget, vol.8, issue.45, pp.79126-79136, 2017.

J. L. Perez-gracia, G. Ruiz-ilundain, M. Garcia-ribas, I. , M. Carrasco et al., The role of extreme phenotype selection studies in the identification of clinically relevant genotypes in cancer research, Cancer, vol.95, issue.7, pp.1605-1610, 2002.

G. Iyer, A. J. Hanrahan, and M. I. Milowsky, Genome sequencing identifies a basis for everolimus sensitivity, Science, vol.338, issue.6104, p.221, 2012.

N. Wagle, B. C. Grabiner, and E. M. Van-allen, Response and acquired resistance to everolimus in anaplastic thyroid cancer, N Engl J Med, vol.371, issue.15, pp.1426-1433, 2014.

E. M. Van-allen, K. W. Mouw, and P. Kim, Somatic ERCC2 mutations correlate with cisplatin sensitivity in muscle-invasive urothelial carcinoma, Cancer Discov, vol.4, issue.10, pp.1140-1153, 2014.

R. Itzykson, S. Thépot, and B. Quesnel, Prognostic factors for response and overall survival in 282 patients with higher-risk myelodysplastic syndromes treated with azacitidine, Blood, vol.117, issue.2, pp.403-411, 2011.

H. Herz, A. Garruss, and A. Shilatifard, SET for life: biochemical activities and biological functions of SET domain-containing proteins, Trends Biochem Sci, vol.38, issue.12, pp.621-639, 2013.

I. Pinheiro, R. Margueron, and N. Shukeir, Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity, Cell, vol.150, issue.5, pp.948-960, 2012.

A. Wanquet, T. Prebet, and C. Berthon, Azacitidine treatment for patients with myelodysplastic syndrome and acute myeloid leukemia with chromosome 3q abnormalities, Am J Hematol, vol.90, issue.10, pp.859-863, 2015.

E. Bindels, M. Havermans, and S. Lugthart, EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs, Blood, vol.119, issue.24, pp.5838-5849, 2012.

Y. Zhang, K. Owens, and L. Hatem, Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia, Blood, vol.122, issue.16, pp.2888-2892, 2013.

A. Monnereau, L. Remontet, and M. Maynadié, Estimation nationale de l'incidence des cancers en France entre 1980 et 2012, p.88, 2013.

O. Visser, A. Trama, and M. Maynadié, Incidence, survival and prevalence of myeloid malignancies in Europe, Eur J Cancer, vol.48, issue.17, pp.3257-3266, 2012.

M. Sant, C. Allemani, and C. Tereanu, Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project, Blood, vol.116, pp.3724-3734, 2010.

F. R. Appelbaum, H. Gundacker, and D. R. Head, Age and acute myeloid leukemia, Blood, vol.107, issue.9, pp.3481-3485, 2006.

G. Østgård, L. S. Medeiros, B. C. Sengeløv, and H. , Epidemiology and Clinical Significance of Secondary and Therapy-Related Acute Myeloid Leukemia: A National Population-Based Cohort Study, J Clin Oncol, vol.33, issue.31, pp.3641-3649, 2015.

E. Hulegårdh, C. Nilsson, and V. Lazarevic, Characterization and prognostic features of secondary acute myeloid leukemia in a population-based setting: a report from the Swedish Acute Leukemia Registry, Am J Hematol, vol.90, issue.3, pp.208-214, 2015.

D. A. Arber, A. Orazi, and R. Hasserjian, The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia, Blood, vol.127, issue.20, pp.2391-2405, 2016.

S. Bertoli, A. Sterin, and S. Tavitian, Therapy-related acute myeloid leukemia following treatment of lymphoid malignancies, Oncotarget, vol.7, issue.52, pp.85937-85947, 2016.

M. Schaapveld, B. Aleman, and A. M. Van-eggermond, Second Cancer Risk Up to 40 Years after Treatment for Hodgkin's Lymphoma, N Engl J Med, vol.373, issue.26, pp.2499-2511, 2015.

L. M. Morton, G. M. Dores, and M. A. Tucker, Evolving risk of therapy-related acute myeloid leukemia following cancer chemotherapy among adults in the United States, Blood, vol.121, issue.15, pp.2996-3004, 1975.

D. Bonnet and J. E. Dick, Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell, Nat Med, vol.3, issue.7, pp.730-737, 1997.

T. Lapidot, C. Sirard, and J. Vormoor, A cell initiating human acute myeloid leukaemia after transplantation into SCID mice, Nature, vol.367, issue.6464, pp.645-648, 1994.

S. J. Horton and B. Huntly, Recent advances in acute myeloid leukemia stem cell biology, Haematologica, vol.97, issue.7, pp.966-974, 2012.

E. Papaemmanuil, M. Gerstung, and L. Malcovati, Clinical and biological implications of driver mutations in myelodysplastic syndromes, Blood, vol.122, issue.22, pp.3616-3627, 2013.

M. J. Walter, D. Shen, and L. Ding, Clonal architecture of secondary acute myeloid leukemia, N Engl J Med, vol.366, issue.12, pp.1090-1098, 2012.

M. Mossner, J. Jann, and J. Wittig, Mutational hierarchies in myelodysplastic syndromes dynamically adapt and evolve upon therapy response and failure, Blood, vol.128, issue.9, pp.1246-1259, 2016.

H. Makishima, T. Yoshizato, and K. Yoshida, Dynamics of clonal evolution in myelodysplastic syndromes, Nat Genet, vol.49, issue.2, pp.204-212, 2017.

P. Da-silva-coelho, L. I. Kroeze, and K. Yoshida, Clonal evolution in myelodysplastic syndromes, Nat Commun, p.815099, 2017.

V. Chesnais, M. Arcangeli, and C. Delette, Architectural and functional heterogeneity of hematopoietic stem/progenitor cells in non-del(5q) myelodysplastic syndromes, Blood, vol.129, issue.4, pp.484-496, 2017.

T. J. Ley and C. Miller, Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia, N Engl J Med, vol.368, issue.22, pp.2059-2074, 2013.

G. Juliusson, P. Antunovic, and A. Derolf, Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry, Blood, vol.113, issue.18, pp.4179-4187, 2009.

V. L. Lazarevic, A. Bredberg, and F. Lorenz, Acute myeloid leukemia in very old patients, Haematologica

E. Papaemmanuil, M. Gerstung, and L. Bullinger, Genomic Classification and Prognosis in Acute Myeloid Leukemia, N Engl J Med, vol.374, issue.23, pp.2209-2221, 2016.

V. V. Prassek, M. Rothenberg-thurley, and M. C. Sauerland, Genetics of acute myeloid leukemia in the elderly: mutation spectrum and clinical impact in intensively treated patients aged ? 75 years, Haematologica

L. Bullinger, K. Döhner, and H. Döhner, Genomics of Acute Myeloid Leukemia Diagnosis and Pathways, J Clin Oncol, vol.35, issue.9, pp.934-946, 2017.

C. Tsai, H. Hou, and J. Tang, Genetic alterations and their clinical implications in older patients with acute myeloid leukemia, Leukemia, vol.30, issue.7, pp.1485-1492, 2016.

F. Ostronoff, M. Othus, and M. Lazenby, Prognostic significance of NPM1 mutations in the absence of FLT3-internal tandem duplication in older patients with acute myeloid leukemia: a SWOG and UK National Cancer Research Institute/Medical Research Council report, J Clin Oncol, vol.33, issue.10, pp.1157-1164, 2015.

N. Daver, T. Liu-dumlao, and F. Ravandi, Effect of NPM1 and FLT3 mutations on the outcomes of elderly patients with acute myeloid leukemia receiving standard chemotherapy, Clin Lymphoma Myeloma Leuk, vol.13, issue.4, pp.435-440, 2013.

C. Thiede, S. Koch, and E. Creutzig, Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML), Blood, vol.107, issue.10, pp.4011-4020, 2006.

B. Falini, C. Mecucci, and E. Tiacci, Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype, N Engl J Med, vol.352, issue.3, pp.254-266, 2005.

K. Döhner, R. F. Schlenk, and M. Habdank, Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations, Blood, vol.106, issue.12, pp.3740-3746, 2005.

C. Haferlach, C. Mecucci, and S. Schnittger, AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features, Blood, vol.114, issue.14, pp.3024-3032, 2009.

M. S. De-propris, S. Raponi, and D. Diverio, High CD33 expression levels in acute myeloid leukemia cells carrying the nucleophosmin (NPM1) mutation, Haematologica, vol.96, issue.10, pp.1548-1551, 2011.

B. Falini, N. Bolli, and A. Liso, Altered nucleophosmin transport in acute myeloid leukaemia with mutated NPM1: molecular basis and clinical implications, Leukemia, vol.23, issue.10, pp.1731-1743, 2009.

W. Den-besten, M. Kuo, R. T. Williams, and C. J. Sherr, Myeloid leukemia-associated nucleophosmin mutants perturb p53-dependent and independent activities of the Arf tumor suppressor protein, Cell Cycle, vol.4, issue.11, pp.1593-1598, 2005.

P. Bonetti, T. Davoli, C. Sironi, B. Amati, P. G. Pelicci et al., Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7 gamma, J Cell Biol, vol.182, issue.1, pp.19-26, 2008.

D. G. Gilliland and J. D. Griffin, The roles of FLT3 in hematopoiesis and leukemia, Blood, vol.100, issue.5, pp.1532-1542, 2002.

M. Levis, K. M. Murphy, and R. Pham, Internal tandem duplications of the FLT3 gene are present in leukemia stem cells, Blood, vol.106, issue.2, pp.673-680, 2005.

M. C. Chillón, C. Santamaría, and R. García-sanz, Long FLT3 internal tandem duplications and reduced PML-RAR? expression at diagnosis characterize a high-risk subgroup of acute promyelocytic leukemia patients, Haematologica, vol.95, issue.5, pp.745-751, 2010.

P. D. Kottaridis, R. E. Gale, and M. E. Frew, The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials, Blood, vol.98, issue.6, pp.1752-1759, 2001.

T. Haferlach, Y. Nagata, and V. Grossmann, Landscape of genetic lesions in 944 patients with myelodysplastic syndromes, Leukemia, vol.28, issue.2, pp.241-247, 2014.

E. Taskesen, M. Havermans, and K. Van-lom, Two splice-factor mutant leukemia subgroups uncovered at the boundaries of MDS and AML using combined gene expression and DNA-methylation profiling, Blood, vol.123, issue.21, pp.3327-3335, 2014.

K. Yoshida, M. Sanada, and Y. Shiraishi, Frequent pathway mutations of splicing machinery in myelodysplasia, Nature, vol.478, issue.7367, pp.64-69, 2011.

T. Okuda, J. Van-deursen, S. W. Hiebert, G. Grosveld, and J. R. Downing, AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis, Cell, vol.84, issue.2, pp.321-330, 1996.

M. Ichikawa, T. Asai, and T. Saito, AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis, Nat Med, vol.10, issue.3, pp.299-304, 2004.

M. Sakurai, H. Kunimoto, and N. Watanabe, Impaired hematopoietic differentiation of RUNX1-mutated induced pluripotent stem cells derived from FPD/AML patients, Leukemia, vol.28, issue.12, pp.2344-2354, 2014.

V. I. Gaidzik, V. Teleanu, and E. Papaemmanuil, RUNX1 mutations in acute myeloid leukemia are associated with distinct clinico-pathologic and genetic features, Leukemia, vol.30, issue.11, pp.2160-2168, 2016.

M. Khan, J. Cortes, and T. Kadia, Clinical Outcomes and Co-Occurring Mutations in Patients with RUNX1-Mutated Acute Myeloid Leukemia, Int J Mol Sci, vol.18, issue.8

J. H. Mendler, K. Maharry, and M. D. Radmacher, RUNX1 mutations are associated with poor outcome in younger and older patients with cytogenetically normal acute myeloid leukemia and with distinct gene and MicroRNA expression signatures, J Clin Oncol, vol.30, issue.25, pp.3109-3118, 2012.

P. A. Greif, N. P. Konstandin, and K. H. Metzeler, RUNX1 mutations in cytogenetically normal acute myeloid leukemia are associated with a poor prognosis and up-regulation of lymphoid genes, Haematologica, vol.97, issue.12, pp.1909-1915, 2012.

S. Adamia, B. Haibe-kains, and P. M. Pilarski, A genome-wide aberrant RNA splicing in patients with acute myeloid leukemia identifies novel potential disease markers and therapeutic targets, Clin Cancer Res, vol.20, issue.5, pp.1135-1145, 2014.

A. M. Mohamed, M. Thénoz, F. Solly, M. Balsat, F. Mortreux et al., How mRNA is misspliced in acute myelogenous leukemia (AML)?, Oncotarget, vol.5, issue.20, pp.9534-9545, 2014.

R. F. Luco, M. Allo, I. E. Schor, A. R. Kornblihtt, and T. Misteli, Epigenetics in alternative premRNA splicing, Cell, vol.144, issue.1, pp.16-26, 2011.

E. Papaemmanuil, M. Cazzola, and J. Boultwood, Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts, N Engl J Med, vol.365, issue.15, pp.1384-1395, 2011.

V. Visconte, H. Makishima, and A. Jankowska, SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts, Leukemia, vol.26, issue.3, pp.542-545, 2012.

L. Malcovati, M. Karimi, and E. Papaemmanuil, SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts, Blood, vol.126, issue.2, pp.233-241, 2015.

H. Hou, C. Liu, and Y. Kuo, Splicing factor mutations predict poor prognosis in patients with de novo acute myeloid leukemia, Oncotarget, vol.7, issue.8, pp.9084-9101, 2016.

G. Grech, J. Pollacco, and M. Portelli, Expression of different functional isoforms in haematopoiesis, Int J Hematol, vol.99, issue.1, pp.4-11, 2014.

C. A. Larsson and G. Cote, Quintás-Cardama A. The changing mutational landscape of acute myeloid leukemia and myelodysplastic syndrome, Mol Cancer Res, vol.11, issue.8, pp.815-827, 2013.

V. Lazarevic, A. Hörstedt, and B. Johansson, Incidence and prognostic significance of karyotypic subgroups in older patients with acute myeloid leukemia: the Swedish population-based experience, Blood Cancer J, 2014.

D. Grimwade, R. K. Hills, and A. V. Moorman, Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials, Blood, vol.116, issue.3, pp.354-365, 2010.

U. Creutzig, M. Zimmermann, and D. Reinhardt, Changes in cytogenetics and molecular genetics in acute myeloid leukemia from childhood to adult age groups, Cancer, vol.122, issue.24, pp.3821-3830, 2016.

S. K. Horrigan, C. A. Westbrook, A. H. Kim, M. Banerjee, W. Stock et al., Polymerase chain reaction-based diagnosis of del (5q) in acute myeloid leukemia and myelodysplastic syndrome identifies a minimal deletion interval, Blood, vol.88, issue.7, pp.2665-2670, 1996.

V. Adema and R. Bejar, What lies beyond del(5q) in myelodysplastic syndrome?, Haematologica, vol.98, issue.12, pp.1819-1821, 2013.

K. Döhner, J. Brown, and U. Hehmann, Molecular cytogenetic characterization of a critical region in bands 7q35-q36 commonly deleted in malignant myeloid disorders, Blood, vol.92, issue.11, pp.4031-4035, 1998.

J. Kere, T. Ruutu, R. Lahtinen, and A. De-la-chapelle, Molecular characterization of chromosome 7 long arm deletions in myeloid disorders, Blood, vol.70, issue.5, pp.1349-1353, 1987.

L. Beau, M. M. Espinosa, R. Davis, E. M. Eisenbart, J. D. Larson et al., Cytogenetic and molecular delineation of a region of chromosome 7 commonly deleted in malignant myeloid diseases, Blood, vol.88, issue.6, pp.1930-1935, 1996.

L. Zhou, J. Opalinska, and D. Sohal, Aberrant epigenetic and genetic marks are seen in myelodysplastic leukocytes and reveal Dock4 as a candidate pathogenic gene on chromosome 7q, J Biol Chem, vol.286, issue.28, pp.25211-25223, 2011.

C. Chen, Y. Liu, and A. R. Rappaport, MLL3 is a haploinsufficient 7q tumor suppressor in acute myeloid leukemia, Cancer Cell, vol.25, issue.5, pp.652-665, 2014.

V. Soenen, C. Preudhomme, C. Roumier, A. Daudignon, J. L. Laï et al., 17p Deletion in acute myeloid leukemia and myelodysplastic syndrome. Analysis of breakpoints and deleted segments by fluorescence in situ, Blood, vol.91, issue.3, pp.1008-1015, 1998.

L. Bouaoun, D. Sonkin, and M. Ardin, TP53 Variations in Human Cancers: New Lessons from the IARC TP53 Database and Genomics Data, Hum Mutat, vol.37, issue.9, pp.865-876, 2016.

B. Vogelstein, D. Lane, and A. J. Levine, Surfing the p53 network, Nature, vol.408, issue.6810, pp.307-310, 2000.

M. Hollstein, D. Sidransky, B. Vogelstein, and C. C. Harris, p53 mutations in human cancers, Science, vol.253, issue.5015, pp.49-53, 1991.

R. Brosh and V. Rotter, When mutants gain new powers: news from the mutant p53 field, Nat Rev Cancer, vol.9, issue.10, pp.701-713, 2009.

Y. Cho, S. Gorina, P. D. Jeffrey, and N. P. Pavletich, Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations, Science, vol.265, issue.5170, pp.346-355, 1994.

H. Seifert, B. Mohr, and C. Thiede, The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia, Leukemia, vol.23, issue.4, pp.656-663, 2009.

D. Chen, J. Yoon, and W. Gu, Reactivating the ARF-p53 axis in AML cells by targeting ULF, Cell Cycle, vol.9, issue.15, pp.2946-2951, 2010.

D. Sasca, P. S. Hähnel, and J. Szybinski, SIRT1 prevents genotoxic stress-induced p53 activation in acute myeloid leukemia, Blood, vol.124, issue.1, pp.121-133, 2014.

S. Peller and V. Rotter, TP53 in hematological cancer: low incidence of mutations with significant clinical relevance, Hum Mutat, vol.21, issue.3, pp.277-284, 2003.

D. Bowen, M. J. Groves, and A. K. Burnett, TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis, Leukemia, vol.23, issue.1, pp.203-206, 2009.

D. P. Steensma, R. Bejar, and S. Jaiswal, Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes, Blood, vol.126, issue.1, pp.9-16, 2015.

A. S. Sperling, C. J. Gibson, and B. L. Ebert, The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia, Nat Rev Cancer, vol.17, issue.1, pp.5-19, 2017.

T. N. Wong, G. Ramsingh, and A. L. Young, Role of TP53 mutations in the origin and evolution of therapy-related acute myeloid leukaemia, Nature, vol.518, issue.7540, pp.552-555, 2015.

K. Sabapathy and D. P. Lane, Therapeutic targeting of p53: all mutants are equal, but some mutants are more equal than others, Nat Rev Clin Oncol, vol.15, issue.1, pp.13-30, 2018.

M. L. Poeta, J. Manola, and M. A. Goldwasser, TP53 mutations and survival in squamouscell carcinoma of the head and neck, N Engl J Med, vol.357, issue.25, pp.2552-2561, 2007.

K. H. Young, D. D. Weisenburger, and B. J. Dave, Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma, Blood, vol.110, issue.13, pp.4396-4405, 2007.

D. M. Neskey, A. A. Osman, and T. J. Ow, Evolutionary Action Score of TP53 Identifies High-Risk Mutations Associated with Decreased Survival and Increased Distant Metastases in Head and Neck Cancer, Cancer Res, vol.75, issue.7, pp.1527-1536, 2015.

E. Kotler, O. Shani, and G. Goldfeld, A Systematic p53 Mutation Library Links Differential Functional Impact to Cancer Mutation Pattern and Evolutionary Conservation, Mol Cell, vol.71, issue.1, pp.178-190, 2018.

S. Lugthart, S. Gröschel, and H. B. Beverloo, Clinical, molecular, and prognostic significance of WHO type inv(3)(q21q26.2)/t(3;3)(q21;q26.2) and various other 3q abnormalities in acute myeloid leukemia, J Clin Oncol, vol.28, issue.24, pp.3890-3898, 2010.

H. J. Rogers, J. W. Vardiman, and J. Anastasi, Complex or monosomal karyotype and not blast percentage is associated with poor survival in acute myeloid leukemia and myelodysplastic syndrome patients with inv(3)(q21q26.2)/t(3;3)(q21;q26.2): a Bone Marrow Pathology Group study, Haematologica, vol.99, issue.5, pp.821-829, 2014.

J. Sun, S. N. Konoplev, and X. Wang, De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification, Mod Pathol, vol.24, issue.3, pp.384-389, 2011.

C. Haferlach, U. Bacher, and T. Haferlach, The inv(3)(q21q26)/t(3;3)(q21;q26) is frequently accompanied by alterations of the RUNX1, KRAS and NRAS and NF1 genes and mediates adverse prognosis both in MDS and in AML: a study in 39 cases of MDS or AML, Leukemia, vol.25, issue.5, pp.874-877, 2011.

V. Lavallée, P. Gendron, S. Lemieux, D. Angelo, G. Hébert et al., EVI1-rearranged acute myeloid leukemias are characterized by distinct molecular alterations, Blood, vol.125, issue.1, pp.140-143, 2015.

A. A. Hinai and P. Valk, Review: Aberrant EVI1 expression in acute myeloid leukaemia, Br J Haematol, vol.172, issue.6, pp.870-878, 2016.

E. Bindels, M. Havermans, and S. Lugthart, EVI1 is critical for the pathogenesis of a subset of MLL-AF9-rearranged AMLs, Blood, vol.119, issue.24, pp.5838-5849, 2012.

O. Abdel-wahab and R. L. Levine, Mutations in epigenetic modifiers in the pathogenesis and therapy of acute myeloid leukemia, Blood, vol.121, issue.18, pp.3563-3572, 2013.

C. Y. Fong, J. Morison, and M. A. Dawson, Epigenetics in the hematologic malignancies, Haematologica, vol.99, issue.12, pp.1772-1783, 2014.

S. M. Greenblatt and S. D. Nimer, Chromatin modifiers and the promise of epigenetic therapy in acute leukemia, Leukemia, vol.28, issue.7, pp.1396-1406, 2014.

M. E. Figueroa, S. Lugthart, and Y. Li, DNA methylation signatures identify biologically distinct subtypes in acute myeloid leukemia, Cancer Cell, vol.17, issue.1, pp.13-27, 2010.

A. Akalin, F. E. Garrett-bakelman, and M. Kormaksson, Base-pair resolution DNA methylation sequencing reveals profoundly divergent epigenetic landscapes in acute myeloid leukemia, PLoS Genet, vol.8, issue.6, p.1002781, 2012.

L. Bullinger, M. Ehrich, and K. Döhner, Quantitative DNA methylation predicts survival in adult acute myeloid leukemia, Blood, vol.115, issue.3, pp.636-642, 2010.

H. X. Meng, J. A. Hackett, and C. Nestor, Apoptosis and DNA methylation, Cancers (Basel), vol.3, issue.2, pp.1798-1820, 2011.

T. J. Ley, L. Ding, and M. J. Walter, DNMT3A mutations in acute myeloid leukemia, N Engl J Med, vol.363, issue.25, pp.2424-2433, 2010.

A. Ribeiro, M. Pratcorona, and C. Erpelinck-verschueren, Mutant DNMT3A: a marker of poor prognosis in acute myeloid leukemia, Blood, vol.119, issue.24, pp.5824-5831, 2012.

X. Yan, J. Xu, and Z. Gu, Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia, Nat Genet, vol.43, issue.4, pp.309-315, 2011.

G. Marcucci, K. H. Metzeler, and S. Schwind, Age-related prognostic impact of different types of DNMT3A mutations in adults with primary cytogenetically normal acute myeloid leukemia, J Clin Oncol, vol.30, issue.7, pp.742-750, 2012.

L. I. Shlush, S. Zandi, and A. Mitchell, Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia, Nature, vol.506, issue.7488, pp.328-333, 2014.

S. Jaiswal, P. Fontanillas, and J. Flannick, Age-related clonal hematopoiesis associated with adverse outcomes, N Engl J Med, vol.371, issue.26, pp.2488-2498, 2014.

D. A. Russler-germain, D. H. Spencer, and M. A. Young, The R882H DNMT3A mutation associated with AML dominantly inhibits wild-type DNMT3A by blocking its ability to form active tetramers, Cancer Cell, vol.25, issue.4, pp.442-454, 2014.

G. A. Challen, D. Sun, and M. Jeong, Dnmt3a is essential for hematopoietic stem cell differentiation, Nat Genet, vol.44, issue.1, pp.23-31, 2011.

H. Celik, C. Mallaney, and A. Kothari, Enforced differentiation of Dnmt3a-null bone marrow leads to failure with c-Kit mutations driving leukemic transformation, Blood, vol.125, issue.4, pp.619-628, 2015.

L. Yang, R. Rau, and M. A. Goodell, DNMT3A in haematological malignancies, Nat Rev Cancer, vol.15, issue.3, pp.152-165, 2015.

M. Tahiliani, K. P. Koh, and Y. Shen, Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1, Science, vol.324, issue.5929, pp.930-935, 2009.

S. Ito, D. 'alessio, A. C. Taranova, O. V. Hong, K. Sowers et al., Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification, Nature, vol.466, issue.7310, pp.1129-1133, 2010.

Y. He, B. Li, and Z. Li, Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA, Science, vol.333, issue.6047, pp.1303-1307, 2011.

R. M. Kohli and Y. Zhang, TET enzymes, TDG and the dynamics of DNA demethylation, Nature, vol.502, issue.7472, pp.472-479, 2013.

R. L. Bowman and R. L. Levine, TET2 in Normal and Malignant Hematopoiesis, Cold Spring Harb Perspect Med, vol.7, issue.8

M. Ko, H. S. Bandukwala, and J. An, Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice, Proc Natl Acad Sci, vol.108, issue.35, pp.14566-14571, 2011.

K. Moran-crusio, L. Reavie, and A. Shih, Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation, Cancer Cell, vol.20, issue.1, pp.11-24, 2011.

C. Quivoron, L. Couronné, D. Valle, and V. , TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis, Cancer Cell, vol.20, issue.1, pp.25-38, 2011.

L. Dang, D. W. White, and S. Gross, Cancer-associated IDH1 mutations produce 2-hydroxyglutarate, Nature, vol.462, issue.7274, pp.739-744, 2009.

P. S. Ward, J. Patel, and D. R. Wise, The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate, Cancer Cell, vol.17, issue.3, pp.225-234, 2010.

M. E. Figueroa, O. Abdel-wahab, and C. Lu, Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation, Cancer Cell, vol.18, issue.6, pp.553-567, 2010.

Y. Wang, M. Xiao, and X. Chen, WT1 recruits TET2 to regulate its target gene expression and suppress leukemia cell proliferation, Mol Cell, vol.57, issue.4, pp.662-673, 2015.

A. Tefferi, A. Pardanani, and K. Lim, TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis, Leukemia, vol.23, issue.5, pp.905-911, 2009.

A. M. Jankowska, H. Szpurka, and R. V. Tiu, Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms, Blood, vol.113, issue.25, pp.6403-6410, 2009.

S. Langemeijer, R. P. Kuiper, and M. Berends, Acquired mutations in TET2 are common in myelodysplastic syndromes, Nat Genet, vol.41, issue.7, pp.838-842, 2009.

F. Delhommeau, S. Dupont, D. Valle, and V. , Mutation in TET2 in myeloid cancers, N Engl J Med, vol.360, issue.22, pp.2289-2301, 2009.

L. Couronné, C. Bastard, and O. A. Bernard, TET2 and DNMT3A mutations in human T-cell lymphoma, N Engl J Med, vol.366, issue.1, pp.95-96, 2012.

A. H. Shih, O. Abdel-wahab, J. P. Patel, and R. L. Levine, The role of mutations in epigenetic regulators in myeloid malignancies, Nat Rev Cancer, vol.12, issue.9, pp.599-612, 2012.

A. H. Shih, Y. Jiang, and C. Meydan, Mutational cooperativity linked to combinatorial epigenetic gain of function in acute myeloid leukemia, Cancer Cell, vol.27, issue.4, pp.502-515, 2015.

V. I. Gaidzik, P. Paschka, and D. Späth, TET2 mutations in acute myeloid leukemia (AML): results from a comprehensive genetic and clinical analysis of the AML study group, J Clin Oncol, vol.30, issue.12, pp.1350-1357, 2012.

E. R. Mardis, L. Ding, and D. J. Dooling, Recurring mutations found by sequencing an acute myeloid leukemia genome, N Engl J Med, vol.361, issue.11, pp.1058-1066, 2009.

A. P. Im, A. R. Sehgal, and M. P. Carroll, DNMT3A and IDH mutations in acute myeloid leukemia and other myeloid malignancies: associations with prognosis and potential treatment strategies, Leukemia, vol.28, issue.9, pp.1774-1783, 2014.

M. Sasaki, C. B. Knobbe, and J. C. Munger, IDH1(R132H) mutation increases murine haematopoietic progenitors and alters epigenetics, Nature, vol.488, issue.7413, pp.656-659, 2012.

S. Weissmann, T. Alpermann, and V. Grossmann, Landscape of TET2 mutations in acute myeloid leukemia, Leukemia, vol.26, issue.5, pp.934-942, 2012.

W. Xu, H. Yang, and Y. Liu, Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of ?-ketoglutarate-dependent dioxygenases, Cancer Cell, vol.19, issue.1, pp.17-30, 2011.

K. H. Metzeler, H. Becker, and K. Maharry, ASXL1 mutations identify a high-risk subgroup of older patients with primary cytogenetically normal AML within the ELN Favorable genetic category, Blood, vol.118, issue.26, pp.6920-6929, 2011.

V. Gelsi-boyer, V. Trouplin, and J. Adélaïde, Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia, Br J Haematol, vol.145, issue.6, pp.788-800, 2009.

J. Boultwood, J. Perry, and A. Pellagatti, Frequent mutation of the polycombassociated gene ASXL1 in the myelodysplastic syndromes and in acute myeloid leukemia, Leukemia, vol.24, issue.5, pp.1062-1065, 2010.

J. Boultwood, J. Perry, and R. Zaman, High-density single nucleotide polymorphism array analysis and ASXL1 gene mutation screening in chronic myeloid leukemia during disease progression, Leukemia, vol.24, issue.6, pp.1139-1145, 2010.

T. Chen, H. Hou, and W. Chou, Dynamics of ASXL1 mutation and other associated genetic alterations during disease progression in patients with primary myelodysplastic syndrome, Blood Cancer J, pp.4-177, 2014.

N. Carbuccia, A. Murati, and V. Trouplin, Mutations of ASXL1 gene in myeloproliferative neoplasms, Leukemia, vol.23, issue.11, pp.2183-2186, 2009.

M. Brecqueville, J. Rey, and F. Bertucci, Mutation analysis of ASXL1, Genes Chromosomes Cancer, vol.51, issue.8, pp.743-755, 2012.

G. Genovese, A. K. Kähler, and R. E. Handsaker, Clonal hematopoiesis and blood-cancer risk inferred from blood DNA sequence, N Engl J Med, vol.371, issue.26, pp.2477-2487, 2014.

R. Nagase, D. Inoue, and A. Pastore, Expression of mutant Asxl1 perturbs hematopoiesis and promotes susceptibility to leukemic transformation, J Exp Med, vol.215, issue.6, pp.1729-1747, 2018.

H. Yang, S. Kurtenbach, and Y. Guo, Gain of function of ASXL1 truncating protein in the pathogenesis of myeloid malignancies, Blood, vol.131, issue.3, pp.328-341, 2018.

V. Gelsi-boyer, V. Trouplin, and J. Roquain, ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia, Br J Haematol, vol.151, issue.4, pp.365-375, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00580698

I. Pinheiro, R. Margueron, and N. Shukeir, Prdm3 and Prdm16 are H3K9me1 methyltransferases required for mammalian heterochromatin integrity, Cell, vol.150, issue.5, pp.948-960, 2012.

L. Busque, J. P. Patel, and M. E. Figueroa, Recurrent somatic TET2 mutations in normal elderly individuals with clonal hematopoiesis, Nat Genet, vol.44, issue.11, pp.1179-1181, 2012.

L. Ding, T. J. Ley, and D. E. Larson, Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing, Nature, vol.481, issue.7382, pp.506-510, 2012.

J. S. Welch, T. J. Ley, and D. C. Link, The origin and evolution of mutations in acute myeloid leukemia, Cell, vol.150, issue.2, pp.264-278, 2012.

M. Buscarlet, S. Provost, and Y. F. Zada, DNMT3A and TET2 dominate clonal hematopoiesis and demonstrate benign phenotypes and different genetic predispositions, Blood, vol.130, issue.6, pp.753-762, 2017.

C. A. Cargo, N. Rowbotham, and P. A. Evans, Targeted sequencing identifies patients with preclinical MDS at high risk of disease progression, Blood, vol.126, issue.21, pp.2362-2365, 2015.

J. M. Bennett, D. Catovsky, and M. T. Daniel, Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group, Br J Haematol, vol.33, issue.4, pp.451-458, 1976.

D. R. Head, Revised classification of acute myeloid leukemia, Leukemia, vol.10, issue.11, pp.1826-1831, 1996.

J. W. Vardiman, J. Thiele, and D. A. Arber, The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes, Blood, vol.114, issue.5, pp.937-951, 2009.

J. L. Krok-schoen, J. L. Fisher, and J. A. Stephens, Incidence and survival of hematological cancers among adults ages ?75 years, Cancer Med

T. Andersson, P. C. Lambert, and A. R. Derolf, Temporal trends in the proportion cured among adults diagnosed with acute myeloid leukaemia in Sweden 1973-2001, a population-based study, Br J Haematol, vol.148, issue.6, pp.918-924, 2010.

M. E. Charlson, P. Pompei, K. L. Ales, and C. R. Mackenzie, A new method of classifying prognostic comorbidity in longitudinal studies: development and validation, J Chronic Dis, vol.40, issue.5, pp.373-383, 1987.

M. L. Sorror, B. M. Sandmaier, and B. E. Storer, Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation, J Clin Oncol, vol.25, issue.27, pp.4246-4254, 2007.

F. J. Giles, G. Borthakur, and F. Ravandi, The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia, Br J Haematol, vol.136, issue.4, pp.624-627, 2007.

K. V. Ballman, Biomarker: Predictive or Prognostic?, J Clin Oncol, vol.33, issue.33, pp.3968-3971, 2015.

D. Grimwade, H. Walker, and G. Harrison, The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial, Blood, vol.98, issue.5, pp.1312-1320, 2001.

V. Lazarevic, A. Hörstedt, and B. Johansson, Failure matters: unsuccessful cytogenetics and unperformed cytogenetics are associated with a poor prognosis in a population-based series of acute myeloid leukaemia, Eur J Haematol, vol.94, issue.5, pp.419-423, 2015.

T. Prébet, N. Boissel, and S. Reutenauer, Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup, J Clin Oncol, vol.27, issue.28, pp.4747-4753, 2009.

F. Mosna, C. Papayannidis, and G. Martinelli, Complex karyotype, older age, and reduced first-line dose intensity determine poor survival in core binding factor acute myeloid leukemia patients with long-term follow-up, Am J Hematol, vol.90, issue.6, pp.515-523, 2015.

G. Ossenkoppele and B. Löwenberg, How I treat the older patient with acute myeloid leukemia, Blood, vol.125, issue.5, pp.767-774, 2015.

A. Perrot, I. Luquet, and A. Pigneux, Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities, Blood, vol.118, issue.3, pp.679-685, 2011.
URL : https://hal.archives-ouvertes.fr/hal-00849657

B. Löwenberg, G. J. Ossenkoppele, and W. Van-putten, High-dose daunorubicin in older patients with acute myeloid leukemia, N Engl J Med, vol.361, issue.13, pp.1235-1248, 2009.

H. Döhner, E. H. Estey, and S. Amadori, Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet, Blood, vol.115, issue.3, pp.453-474, 2010.

H. Döhner, E. Estey, and D. Grimwade, Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel, Blood, vol.129, issue.4, pp.424-447, 2017.

J. Tang, H. Hou, and C. Chen, AML1/RUNX1 mutations in 470 adult patients with de novo acute myeloid leukemia: prognostic implication and interaction with other gene alterations, Blood, vol.114, issue.26, pp.5352-5361, 2009.

M. Pratcorona, S. Abbas, and M. A. Sanders, Acquired mutations in ASXL1 in acute myeloid leukemia: prevalence and prognostic value, Haematologica, vol.97, issue.3, pp.388-392, 2012.

S. Schnittger, C. Eder, and S. Jeromin, ASXL1 exon 12 mutations are frequent in AML with intermediate risk karyotype and are independently associated with an adverse outcome, Leukemia, vol.27, issue.1, pp.82-91, 2013.

F. G. Rücker, R. F. Schlenk, and L. Bullinger, TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome, Blood, vol.119, issue.9, pp.2114-2121, 2012.

R. Devillier, V. Mansat-de-mas, and V. Gelsi-boyer, Role of ASXL1 and TP53 mutations in the molecular classification and prognosis of acute myeloid leukemias with myelodysplasia-related changes, Oncotarget, vol.6, issue.10, pp.8388-8396, 2015.

C. D. Dinardo, E. M. Stein, and S. De-botton, Durable Remissions with Ivosidenib in IDH1-Mutated Relapsed or Refractory AML, N Engl J Med, vol.378, issue.25, pp.2386-2398, 2018.

E. M. Stein, C. D. Dinardo, and D. A. Pollyea, Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia, Blood, vol.130, issue.6, pp.722-731, 2017.

C. P. Leith, K. J. Kopecky, and J. Godwin, Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study, Blood, vol.89, issue.9, pp.3323-3329, 1997.

S. Kayser, K. Döhner, and J. Krauter, The impact of therapy-related acute myeloid leukemia (AML) on outcome in 2853 adult patients with newly diagnosed AML, Blood, vol.117, issue.7, pp.2137-2145, 2011.

M. A. Sekeres, R. M. Stone, and D. Zahrieh, Decision-making and quality of life in older adults with acute myeloid leukemia or advanced myelodysplastic syndrome, Leukemia, vol.18, issue.4, pp.809-816, 2004.

D. Pulte, A. Gondos, and H. Brenner, Improvements in survival of adults diagnosed with acute myeloblastic leukemia in the early 21st century, Haematologica, vol.93, issue.4, pp.594-600, 2008.

A. Burnett, M. Wetzler, and B. Löwenberg, Therapeutic advances in acute myeloid leukemia, J Clin Oncol, vol.29, issue.5, pp.487-494, 2011.

S. Bertoli, S. Tavitian, and A. Huynh, Improved outcome for AML patients over the years 2000-2014, Blood Cancer J, vol.7, issue.12, p.635, 2017.

H. Bower, T. Andersson, M. Björkholm, P. W. Dickman, P. C. Lambert et al., Continued improvement in survival of acute myeloid leukemia patients: an application of the loss in expectation of life, Blood Cancer J, pp.6-390, 2016.

M. Yanada, G. Garcia-manero, G. Borthakur, F. Ravandi, H. Kantarjian et al., Relapse and death during first remission in acute myeloid leukemia, Haematologica, vol.93, issue.4, pp.633-634, 2008.

I. Hubeek, R. W. Stam, and G. J. Peters, The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia, Br J Cancer, vol.93, issue.12, pp.1388-1394, 2005.

Y. Huang, P. Anderle, and K. J. Bussey, Membrane transporters and channels: role of the transportome in cancer chemosensitivity and chemoresistance, Cancer Res, vol.64, issue.12, pp.4294-4301, 2004.

T. Lee, M. Karon, and R. L. Momparler, Kinetic studies on phosphorylation of 5-azacytidine with the purified uridine-cytidine kinase from calf thymus, Cancer Res, vol.34, issue.10, pp.2482-2488, 1974.

P. A. Jones and S. M. Taylor, Cellular differentiation, cytidine analogs and DNA methylation, Cell, vol.20, issue.1, pp.85-93, 1980.

J. Jasielec, V. Saloura, and L. A. Godley, The mechanistic role of DNA methylation in myeloid leukemogenesis, Leukemia, vol.28, issue.9, pp.1765-1773, 2014.

L. H. Li, E. J. Olin, H. H. Buskirk, and L. M. Reineke, Cytotoxicity and mode of action of 5-azacytidine on L1210 leukemia, Cancer Res, vol.30, issue.11, pp.2760-2769, 1970.

J. Datta, K. Ghoshal, T. Motiwala, and J. St, Novel Insights into the Molecular Mechanism of Action of DNA Hypomethylating Agents: Role of Protein Kinase C ? in Decitabine-Induced Degradation of DNA Methyltransferase 1, Genes Cancer, vol.3, issue.1, pp.71-81, 2012.

S. M. Taylor and P. A. Jones, Multiple new phenotypes induced in 10T1/2 and 3T3 cells treated with 5-azacytidine, Cell, vol.17, issue.4, pp.771-779, 1979.

L. R. Silverman, E. P. Demakos, and B. L. Peterson, Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B, J Clin Oncol, vol.20, issue.10, pp.2429-2440, 2002.

L. R. Silverman, D. R. Mckenzie, and B. L. Peterson, Further analysis of trials with azacitidine in patients with myelodysplastic syndrome: studies 8421, 8921, and 9221 by the Cancer and Leukemia Group B, J Clin Oncol, vol.24, issue.24, pp.3895-3903, 2006.

H. Becker, S. Suciu, and B. H. Rüter, Decitabine versus best supportive care in older patients with refractory anemia with excess blasts in transformation (RAEBt) -results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group (GMDSSG), Ann Hematol, vol.94, issue.12, pp.2003-2013, 2015.

J. Issa, G. Roboz, and D. Rizzieri, Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study, Lancet Oncol, vol.16, issue.9, pp.1099-1110, 2015.

D. A. Pollyea, H. E. Kohrt, and L. Gallegos, Safety, efficacy and biological predictors of response to sequential azacitidine and lenalidomide for elderly patients with acute myeloid leukemia, Leukemia, vol.26, issue.5, pp.893-901, 2012.

A. O. Soriano, H. Yang, and S. Faderl, Safety and clinical activity of the combination of 5-azacytidine, valproic acid, and all-trans retinoic acid in acute myeloid leukemia and myelodysplastic syndrome, Blood, vol.110, issue.7, pp.2302-2308, 2007.

E. Raffoux, A. Cras, and C. Recher, Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome, Oncotarget, vol.1, issue.1, pp.34-42, 2010.

T. Prebet, Z. Sun, and M. E. Figueroa, Prolonged administration of azacitidine with or without entinostat for myelodysplastic syndrome and acute myeloid leukemia with myelodysplasia-related changes: results of the US Leukemia Intergroup trial E1905, J Clin Oncol, vol.32, issue.12, pp.1242-1248, 2014.

L. Adès, M. A. Sekeres, and A. Wolfromm, Predictive factors of response and survival among chronic myelomonocytic leukemia patients treated with azacitidine, Leuk Res, vol.37, issue.6, pp.609-613, 2013.

L. H. Van-der-helm, C. Alhan, and P. W. Wijermans, Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme, Br J Haematol, vol.155, issue.5, pp.599-606, 2011.

M. Rius, C. Stresemann, and D. Keller, Human concentrative nucleoside transporter 1-mediated uptake of 5-azacytidine enhances DNA demethylation, Mol Cancer Ther, vol.8, issue.1, pp.225-231, 2009.

V. L. Damaraju, D. Mowles, and S. Yao, Role of human nucleoside transporters in the uptake and cytotoxicity of azacitidine and decitabine, Nucleosides Nucleotides Nucleic Acids, vol.31, issue.3, pp.236-255, 2012.

T. Qin, J. Jelinek, J. Si, J. Shu, and J. Issa, Mechanisms of resistance to 5-aza-2'-deoxycytidine in human cancer cell lines, Blood, vol.113, issue.3, pp.659-667, 2009.

F. Ravandi, J. Issa, and G. Garcia-manero, Superior outcome with hypomethylating therapy in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome and chromosome 5 and 7 abnormalities, Cancer, vol.115, issue.24, pp.5746-5751, 2009.

E. K. Ritchie, E. J. Feldman, and P. J. Christos, Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia, Leuk Lymphoma, vol.54, issue.9, pp.2003-2007, 2013.

E. Viré, C. Brenner, and R. Deplus, The Polycomb group protein EZH2 directly controls DNA methylation, Nature, vol.439, issue.7078, pp.871-874, 2006.

H. Honda, A. Nagamachi, and T. Inaba, /7q-syndrome in myeloid-lineage hematopoietic malignancies: attempts to understand this complex disease entity, Oncogene, vol.34, issue.7, pp.2413-2425, 2015.

M. Lübbert, B. H. Rüter, and R. Claus, A multicenter phase II trial of decitabine as firstline treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy, Haematologica, vol.97, issue.3, pp.393-401, 2012.

M. Lübbert, S. Suciu, and A. Hagemeijer, Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group, Ann Hematol, vol.95, issue.2, pp.191-199, 2016.

K. Halaburda, M. Labopin, and M. Houhou, AlloHSCT for inv(3)(q21;q26)/t(3;3)(q21;q26) AML: a report from the acute leukemia working party of the European society for blood and marrow transplantation, Bone Marrow Transplant, vol.53, issue.6, pp.683-691, 2018.

T. Braun, R. Itzykson, and A. Renneville, Molecular predictors of response to decitabine in advanced chronic myelomonocytic leukemia: a phase 2 trial, Blood, vol.118, issue.14, pp.3824-3831, 2011.

F. Traina, V. Visconte, and P. Elson, Impact of molecular mutations on treatment response to DNMT inhibitors in myelodysplasia and related neoplasms, Leukemia, vol.28, issue.1, pp.78-87, 2014.

S. Jung, Y. Kim, and S. Yim, Somatic mutations predict outcomes of hypomethylating therapy in patients with myelodysplastic syndrome, Oncotarget, vol.7, issue.34, pp.55264-55275, 2016.

K. H. Metzeler, A. Walker, and S. Geyer, DNMT3A mutations and response to the hypomethylating agent decitabine in acute myeloid leukemia, Leukemia, vol.26, issue.5, pp.1106-1107, 2012.

M. T. Voso, E. Fabiani, and A. Piciocchi, Role of BCL2L10 methylation and TET2 mutations in higher risk myelodysplastic syndromes treated with 5-azacytidine, Leukemia, vol.25, issue.12, pp.1910-1913, 2011.

R. Bejar, A. Lord, and K. Stevenson, TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients, Blood, vol.124, issue.17, pp.2705-2712, 2014.

M. T. Cedena, I. Rapado, and A. Santos-lozano, Mutations in the DNA methylation pathway and number of driver mutations predict response to azacitidine in myelodysplastic syndromes, Oncotarget, vol.8, issue.63, pp.106948-106961, 2017.

T. M. Kadia, P. Jain, and F. Ravandi, TP53 mutations in newly diagnosed acute myeloid leukemia: Clinicomolecular characteristics, response to therapy, and outcomes, Cancer

J. M. Middeke, S. Herold, and E. Rücker-braun, TP53 mutation in patients with highrisk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation, Br J Haematol, vol.172, issue.6, pp.914-922, 2016.

S. O. Ciurea, A. Chilkulwar, and R. M. Saliba, Prognostic factors influencing survival after allogeneic transplantation for AML/MDS patients with TP53 mutations, Blood, vol.131, issue.26, pp.2989-2992, 2018.

L. Yi, Y. Sun, and A. Levine, Selected drugs that inhibit DNA methylation can preferentially kill p53 deficient cells, Oncotarget, vol.5, pp.8924-8936, 2014.

M. Nieto, E. Samper, M. F. Fraga, G. De-buitrago, G. Esteller et al., The absence of p53 is critical for the induction of apoptosis by 5-aza-2'-deoxycytidine, Oncogene, vol.23, issue.3, pp.735-743, 2004.

D. S. Hawkins, G. W. Demers, and D. A. Galloway, Inactivation of p53 enhances sensitivity to multiple chemotherapeutic agents, Cancer Res, vol.56, issue.4, pp.892-898, 1996.

M. L. Smith, J. M. Ford, and M. C. Hollander, p53-mediated DNA repair responses to UV radiation: studies of mouse cells lacking p53, p21, and/or gadd45 genes, Mol Cell Biol, vol.20, issue.10, pp.3705-3714, 2000.

B. C. Mckay, C. Becerril, and M. Ljungman, P53 plays a protective role against UV-and cisplatin-induced apoptosis in transcription-coupled repair proficient fibroblasts, Oncogene, vol.20, issue.46, pp.6805-6808, 2001.

J. Lips and B. Kaina, DNA double-strand breaks trigger apoptosis in p53-deficient fibroblasts, Carcinogenesis, vol.22, issue.4, pp.579-585, 2001.

J. S. Welch, A. A. Petti, and C. A. Miller, TP53 and Decitabine in Acute Myeloid Leukemia and Myelodysplastic Syndromes, N Engl J Med, vol.375, issue.21, pp.2023-2036, 2016.

K. Raj, A. John, and A. Ho, CDKN2B methylation status and isolated chromosome 7 abnormalities predict responses to treatment with 5-azacytidine, Leukemia, vol.21, issue.9, pp.1937-1944, 2007.

M. Daskalakis, T. T. Nguyen, and C. Nguyen, Demethylation of a hypermethylated P15/INK4B gene in patients with myelodysplastic syndrome by 5-Aza-2'-deoxycytidine (decitabine) treatment, Blood, vol.100, issue.8, pp.2957-2964, 2002.

S. D. Gore, S. Baylin, and E. Sugar, Combined DNA methyltransferase and histone deacetylase inhibition in the treatment of myeloid neoplasms, Cancer Res, vol.66, issue.12, pp.6361-6369, 2006.

T. Cluzeau, G. Robert, and N. Mounier, BCL2L10 is a predictive factor for resistance to azacitidine in MDS and AML patients, Oncotarget, vol.3, issue.4, pp.490-501, 2012.

L. Shen, H. Kantarjian, and Y. Guo, DNA methylation predicts survival and response to therapy in patients with myelodysplastic syndromes, J Clin Oncol, vol.28, issue.4, pp.605-613, 2010.

A. S. Yang, K. D. Doshi, and S. Choi, DNA methylation changes after 5-aza-2'-deoxycytidine therapy in patients with leukemia, Cancer Res, vol.66, issue.10, pp.5495-5503, 2006.

H. Kantarjian, Y. Oki, and G. Garcia-manero, Results of a randomized study of 3 schedules of low-dose decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia, Blood, vol.109, issue.1, pp.52-57, 2007.

P. Yan, D. Frankhouser, and M. Murphy, Genome-wide methylation profiling in decitabine-treated patients with acute myeloid leukemia, Blood, vol.120, issue.12, pp.2466-2474, 2012.

M. T. Voso, V. Santini, and E. Fabiani, Why methylation is not a marker predictive of response to hypomethylating agents, Haematologica, vol.99, issue.4, pp.613-619, 2014.

C. Niederwieser, J. Kohlschmidt, and S. Volinia, Prognostic and biologic significance of DNMT3B expression in older patients with cytogenetically normal primary acute myeloid leukemia, Leukemia, vol.29, issue.3, pp.567-575, 2015.

L. Simó-riudalbas, S. A. Melo, and M. Esteller, DNMT3B gene amplification predicts resistance to DNA demethylating drugs, Genes Chromosomes Cancer, vol.50, issue.7, pp.527-534, 2011.

Z. Yang, T. Kondo, and C. S. Voorhorst, Increased c-Jun expression and reduced GATA2 expression promote aberrant monocytic differentiation induced by activating PTPN11 mutants, Mol Cell Biol, vol.29, issue.16, pp.4376-4393, 2009.

R. G. Ramsay and T. J. Gonda, MYB function in normal and cancer cells, Nat Rev Cancer, vol.8, issue.7, pp.523-534, 2008.

V. Ghanim, H. Herrmann, and G. Heller, 5-azacytidine and decitabine exert proapoptotic effects on neoplastic mast cells: role of FAS-demethylation and FAS reexpression, and synergism with FAS-ligand, Blood, vol.119, issue.18, pp.4242-4252, 2012.

S. Ettou, E. Audureau, and C. Humbrecht, Fas expression at diagnosis as a biomarker of azacitidine activity in high-risk MDS and secondary AML, Leukemia, vol.26, issue.10, pp.2297-2299, 2012.
URL : https://hal.archives-ouvertes.fr/hal-01004302

R. Garzon, S. Liu, and M. Fabbri, MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1, Blood, vol.113, issue.25, pp.6411-6418, 2009.

M. Fabbri, R. Garzon, and A. Cimmino, MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B, Proc Natl Acad Sci, vol.104, issue.40, pp.15805-15810, 2007.

W. Blum, R. Garzon, and R. B. Klisovic, Clinical response and miR-29b predictive significance in older AML patients treated with a 10-day schedule of decitabine, Proc Natl Acad Sci, vol.107, issue.16, pp.7473-7478, 2010.

, Annexes Matériel supplémentaire article#1, Bories et al, Am J, 2014174.

, Matériel supplémentaire article#2, Bories et al, Haematologica, pp.2018-179

, Matériel supplémentaire article#3, Bories et al, soumis Blood Cancer Journal???????????, p.193

, Matériel supplémentaire article#4, Bories et al, manuscrit en préparation?????????????

, Annexe I : Matériel supplémentaire article#1, Bories et al, AJH, 2014.

, In which hospital do you practice? (optional question) Please write your answer here

, What is your current position? ? Head of department, professor or assistant professor

, You just have to decide as if you were really facing this choice task 8, Choice, vol.1