D. Pulte, M. Redaniel, L. Jansen, H. Brenner, and M. Jeffreys, Recent trends in survival of adult patients with acute leukemia: overall improvements, but persistent and partly increasing disparity in survival of patients from minority groups, Haematologica, vol.98, issue.2, pp.222-908, 2012.
DOI : 10.3324/haematol.2012.063602

T. Lapidot, C. Sirard, J. Vormoor, B. Murdoch, T. Hoang et al., A cell initiating human acute myeloid leukaemia after transplantation into SCID mice, Nature, vol.367, issue.6464, pp.645-653, 1994.
DOI : 10.1038/367645a0

W. Chan and B. Huntly, Leukemia Stem Cells in Acute Myeloid Leukemia, Seminars in Oncology, vol.35, issue.4, pp.326-361, 2008.
DOI : 10.1053/j.seminoncol.2008.04.003

U. Bacher, S. Schnittger, and T. Haferlach, Molecular genetics in acute myeloid leukemia, Current Opinion in Oncology, vol.22, issue.6, pp.646-55
DOI : 10.1097/CCO.0b013e32833ed806

G. Marcucci, T. Haferlach, and H. Dohner, Molecular Genetics of Adult Acute Myeloid Leukemia: Prognostic and Therapeutic Implications, Journal of Clinical Oncology, vol.29, issue.5, pp.475-86
DOI : 10.1200/JCO.2010.30.2554

D. Gilliland, C. Jordan, and C. Felix, The molecular basis of leukemia. Hematology / the Education Program of the, pp.80-97, 2004.

Y. Yamamoto, H. Kiyoi, Y. Nakano, R. Suzuki, Y. Kodera et al., Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies, Blood, vol.97, issue.8, 2001.
DOI : 10.1182/blood.V97.8.2434

R. Zheng, M. Levis, O. Piloto, P. Brown, B. Baldwin et al., FLT3 ligand causes autocrine signaling in acute myeloid leukemia cells, Blood, vol.103, issue.1, pp.267-74, 2003.
DOI : 10.1182/blood-2003-06-1969

M. Caligiuri, R. Briesewitz, Y. J. Wang, L. Wei, M. Arnoczky et al., Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD Kit receptor dimerization is driven by bivalent binding of stem cell factor Expression of the C-kit receptor (CD117) is a feature of almost all subtypes of de novo acute myeloblastic leukemia (AML), including cytogenetically good-risk AML, and lacks prognostic significance A new twist in the transmembrane signaling tool-kit KIT exon 8 mutations associated with core-binding factor (CBF)-acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor Signal transducer and activator of transcription 3 activation is required for Asp(816) mutant c-Kit-mediated cytokine-independent survival and proliferation in human leukemia cells STAT3 activation is required for Asp(816) mutant c-Kit induced tumorigenicity K-RasG12D expression induces hyperproliferation and aberrant signaling in primary hematopoietic stem/progenitor cells Implications of NRAS mutations in AML: a study of 2502 patients The Journal of clinical investigation, HOX gene regulation in acute myeloid leukemia: CDX marks the spot? Cell cycle Mll partial tandem duplication induces aberrant Hox expression in vivo via specific epigenetic alterations, pp.1022-41339, 1997.

M. Simon, V. Grandage, D. Linch, A. Khwaja, F. Constitutive-rosenbauer et al., Transcription factors in myeloid development: balancing differentiation with transformation Nuclear factorkappaB is constitutively activated in primitive human acute myelogenous leukemia cells The sesquiterpene lactone parthenolide induces apoptosis of human acute myelogenous leukemia stem and progenitor cells Impact of new prognostic markers in treatment decisions in acute myeloid leukemia Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features Gene expression with prognostic implications in cytogenetically normal acute myeloid leukemia Mutations with loss of heterozygosity of p53 are common in therapy-related myelodysplasia and acute myeloid leukemia after exposure to alkylating agents and significantly associated with deletion or loss of 5q, a complex karyotype, and a poor prognosis Epigenetics in acute myeloid leukemia Methylation matters, Oncogene. Epub Nature reviews Immunology. Blood. Blood. Current opinion in hematology. Blood. Seminars in oncology. Epub Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Seminars in oncology. Journal of medical genetics, vol.24730981010516109351219351238, issue.305, pp.2410-20105, 2001.

M. Figueroa, O. Abdel-wahab, C. Lu, P. Ward, J. Patel et al., Leukemic IDH1 and IDH2 Mutations Result in??a Hypermethylation Phenotype, Disrupt TET2 Function, and Impair Hematopoietic Differentiation, Cancer Cell, vol.18, issue.6, pp.553-6707, 2001.
DOI : 10.1016/j.ccr.2010.11.015

D. Croce, L. Raker, V. Corsaro, M. Fazi, F. Fanelli et al., Methyltransferase Recruitment and DNA Hypermethylation of Target Promoters by an Oncogenic Transcription Factor, Science, vol.295, issue.5557, pp.1079-82, 2002.
DOI : 10.1126/science.1065173

S. Liu, T. Shen, L. Huynh, M. Klisovic, L. Rush et al., Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemia. Cancer researchR)-2- hydroxyglutarate is sufficient to promote leukemogenesis and its effects are reversible Do reactive oxygen species play a role in myeloid leukemias? al. Ras-induced reactive oxygen species promote growth factor-independent proliferation in human CD34+ hematopoietic progenitor cells, Science Blood. Blood, vol.653391171151217, issue.37, pp.1277-841621, 2005.

O. Abdel-wahab, R. Levine, J. Bennett, D. Catovsky, M. Daniel et al., Proposals for the classification of the acute leukaemias. French-American-British (FAB) co-operative group British journal of haematology Proposed revised criteria for the classification of acute myeloid leukemia. A report of the French-American- British Cooperative Group World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting-Airlie House Cytogenetics in acute leukemia Blood reviews, Annals of internal medicine. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol.207331031718, issue.42, pp.677-80451, 1976.

K. C. Mrozek, J. Patel, M. Gonen, M. Figueroa, H. Fernandez et al., Seminars in oncology Prognostic relevance of integrated genetic profiling in acute myeloid leukemia Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia, The New England journal of medicine. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol.3512366211216, issue.431224, pp.365-771079, 2003.

E. Berman, G. Heller, J. Santorsa, S. Mckenzie, T. Gee et al., Results of a randomized trial comparing idarubicin and cytosine arabinoside with daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia Cytarabine plus idarubicin or daunorubicin as induction and consolidation therapy for previously untreated adult patients with acute myeloid leukemia Lo-Coco F. Modern approaches to treating acute promyelocytic leukemia, Blood. Blood. Epub Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol.777929, issue.825, pp.1666-74313, 1991.

M. Barnett, R. Bassan, G. Gatta, C. Tondini, and W. Kern, Ferrara F. Treatment of unfit patients with acute myeloid leukemia: a still open clinical challenge Clinical lymphoma, myeloma & leukemia Adult acute myeloid leukaemia, Critical reviews in oncologyhematology, vol.121150, issue.50, pp.10-6197, 2004.

D. Grimwade, H. Walker, F. Oliver, K. Wheatley, C. Harrison et al., The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties, Blood, vol.92, issue.7, pp.2322-2355, 1998.

C. Thiede, C. Steudel, B. Mohr, M. Schaich, U. Schakel et al., Analysis of FLT3- activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia Nucleophosmin gene mutations are predictors of favorable prognosis in acute myelogenous leukemia with a normal karyotype, Blood. Blood. Epub Blood, vol.9911110106, issue.12512, pp.4326-352776, 2002.

C. Thiede, S. Koch, E. Creutzig, C. Steudel, T. Illmer et al., Prevalence and prognostic impact of NPM1 mutations in 1485 adult patients with acute myeloid leukemia (AML) Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia Molecular signatures in acute myeloid leukemia Involvement of oxidative stress in the relapse of acute myeloid leukemia, Blood. The New England journal of medicine. Current opinion in hematology. Epub The Journal of biological chemistry, vol.1073581627285, issue.58, pp.4011-201909, 2006.

F. Zhang, W. Wang, Y. Tsuji, S. Torti, and F. Torti, Post-transcriptional Modulation of Iron Homeostasis during p53-dependent Growth Arrest, Journal of Biological Chemistry, vol.283, issue.49, pp.33911-830, 2008.
DOI : 10.1074/jbc.M806432200

Y. Yu, Z. Kovacevic, and D. Richardson, Tuning Cell Cycle Regulation with an Iron Key, Cell Cycle, vol.6, issue.16, pp.1982-94, 2007.
DOI : 10.4161/cc.6.16.4603

J. Wang and K. Pantopoulos, Regulation of cellular iron metabolism. The Biochemical journal, Epub, vol.43426, issue.302, pp.365-81, 2011.

B. Halliwell, Sies H. Oxidative stress: oxidants and antioxidants, Biochemistry of oxidative stress. Biochemical Society transactions. Epub Experimental physiology, vol.3582, pp.1147-50, 1997.

G. Anderson, D. Frazer, and G. Mclaren, Iron absorption and metabolism. Current opinion in gastroenterology, Epub, vol.2517, issue.64, pp.129-164, 2009.

W. Breuer, M. Shvartsman, Z. Cabantchik, V. Hower, P. Mendes et al., Intracellular labile iron A general map of iron metabolism and tissue-specific subnetworks. Molecular bioSystems Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization Regulation of iron metabolism by hepcidin. Annual review of nutrition Molecular control of vertebrate iron homeostasis by iron regulatory proteins, Science Epub Biochimica et biophysica acta, vol.4052230610302620176329, issue.677, pp.350-4422, 2004.

M. Sanchez, B. Galy, T. Dandekar, P. Bengert, Y. Vainshtein et al., Iron Regulation and the Cell Cycle: IDENTIFICATION OF AN IRON-RESPONSIVE ELEMENT IN THE 3'-UNTRANSLATED REGION OF HUMAN CELL DIVISION CYCLE 14A mRNA BY A REFINED MICROARRAY-BASED SCREENING STRATEGY, Journal of Biological Chemistry, vol.281, issue.32, pp.22865-7409, 2006.
DOI : 10.1074/jbc.M603876200

J. Dupuy, A. Volbeda, P. Carpentier, C. Darnault, J. Moulis et al., Crystal structure of human iron regulatory protein 1 as cytosolic aconitase Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. The Journal of biological chemistry Control of iron homeostasis by an iron-regulated ubiquitin ligase An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis, Structure Science Epub Science, vol.14270326326, issue.73595309, pp.129-3921645, 1993.

K. Zumbrennen, M. Wallander, S. Romney, E. Leibold, M. Ivan et al., Cysteine oxidation regulates the RNA-binding activity of iron regulatory protein 2. Molecular and cellular biology HIFalpha targeted for VHLmediated destruction by proline hydroxylation: implications for O2 sensing Mammalian tissue oxygen levels modulate ironregulatory protein activities in vivo Effects of iron regulatory protein regulation on iron homeostasis during hypoxia, Science Science Epub Blood. Foot LM, vol.29292306121810227413, issue.7798, pp.2219-29464, 1999.

S. Recalcati, G. Minotti, G. Cairo, K. Pantopoulos, M. Hentze et al., Iron regulatory proteins: from molecular mechanisms to drug development Rapid responses to oxidative stress mediated by iron regulatory protein. The EMBO journal Peroxynitrite and nitric oxide differently target the iron-sulfur cluster and amino acid residues of human iron regulatory protein 1 Iron regulatory proteins are essential for intestinal function and control key iron absorption molecules in the duodenum, Antioxidants & redox signaling. Biochemistry. Epub Cell metabolism, vol.131442257, issue.83, pp.1593-6162917, 1995.

W. Wang, X. Di, D. Agostino, R. , J. Torti et al., Excess capacity of the iron regulatory protein system Altered body iron distribution and microcytosis in mice deficient in iron regulatory protein 2 (IRP2), The Journal of biological chemistry. Blood, vol.282106, issue.347, pp.24650-92580, 2005.

P. Aguilar-martinez, J. Schved, P. Brissot, M. Cazzola, G. Bergamaschi et al., The evaluation of hyperferritinemia: an updated strategy based on advances in detecting genetic abnormalities. The American journal of gastroenterology Hereditary hyperferritinemia-cataract syndrome: relationship between phenotypes and specific mutations in the iron-responsive element of ferritin light-chain mRNA, Blood, vol.100229015, issue.88, pp.1185-94814, 1997.

W. Liu, S. Shimomura, H. Imanishi, Y. Iwamoto, N. Ikeda et al., Hemochromatosis with Mutation of the Ferroportin 1 (IREG1) Gene, Internal Medicine, vol.44, issue.4, pp.285-294, 2005.
DOI : 10.2169/internalmedicine.44.285

C. Dycke, P. Charbonnier, K. Pantopoulos, and J. Moulis, A role for lysosomes in the turnover of human iron regulatory protein 2. The international journal of biochemistry & cell biology, pp.2826-2858, 2008.
URL : https://hal.archives-ouvertes.fr/hal-00382015

C. Maffettone, G. Chen, I. Drozdov, C. Ouzounis, and K. Pantopoulos, Tumorigenic Properties of Iron Regulatory Protein 2 (IRP2) Mediated by Its Specific 73-Amino Acids Insert, PLoS ONE, vol.5, issue.4, p.91, 2010.
DOI : 10.1371/journal.pone.0010163.s009

G. Chen, C. Fillebeen, J. Wang, and K. Pantopoulos, Overexpression of iron regulatory protein 1 suppresses growth of tumor xenografts, Carcinogenesis, vol.28, issue.4, pp.785-91, 2006.
DOI : 10.1093/carcin/bgl210

N. Sposi, L. Cianetti, E. Tritarelli, E. Pelosi, S. Militi et al., Mechanisms of differential transferrin receptor expression in normal hematopoiesis, European Journal of Biochemistry, vol.89, issue.23, pp.6762-74, 2000.
DOI : 10.1046/j.1432-1033.2000.01769.x

S. Anderson, C. Nizzi, Y. Chang, K. Deck, P. Schmidt et al., The IRP1-HIF-2alpha axis coordinates iron and oxygen sensing with erythropoiesis and iron absorption, Cell metabolism, vol.1712, issue.2, pp.282-90, 2013.

L. Cianetti, P. Segnalini, A. Calzolari, O. Morsilli, F. Felicetti et al., Expression of alternative transcripts of ferroportin-1 during human erythroid differentiation Remodeling the regulation of iron metabolism during erythroid differentiation to ensure efficient heme biosynthesis Iron-regulatory proteins limit hypoxiainducible factor-2alpha expression in iron deficiency The hematopoietic stem cell niche: low in oxygen but a nice place to be, Epub 2005/12/07. 95. Schranzhofer M, pp.1595-6064159, 2005.

Y. Jang, S. Sharkis, D. Fu, J. Phang, and D. Richardson, A low level of reactive oxygen species selects for primitive hematopoietic stem cells that may reside in the low-oxygenic niche Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression, Blood. Blood, vol.110109, issue.8901, pp.3056-634045, 2007.

J. Ohyashiki, C. Kobayashi, R. Hamamura, S. Okabe, T. Tauchi et al., The oral iron chelator deferasirox represses signaling through the mTOR in myeloid leukemia cells by enhancing expression of REDD1. Cancer science, pp.970-977, 2009.

M. Tschan, D. Shan, J. Laedrach, M. Eyholzer, E. Leibundgut et al., NDRG1/2 expression is inhibited in primary acute myeloid leukemia, Leukemia Research, vol.34, issue.3, pp.393-401, 2009.
DOI : 10.1016/j.leukres.2009.08.037

E. Pourcelot, N. Mobilia, A. Donzé, F. Louis, O. Maler et al., Cellular iron regulation in animals: need and use of suitable models, 2012.

K. Ito, A. Hirao, F. Arai, S. Matsuoka, K. Takubo et al., Regulation of oxidative stress by ATM is required for self-renewal of haematopoietic stem cells, Nature, vol.89, issue.7011, pp.997-100222, 2004.
DOI : 10.1038/35102167

A. Sallmyr, J. Fan, K. Datta, K. Kim, D. Grosu et al., Internal tandem duplication of FLT3 (FLT3/ITD) induces increased ROS production, DNA damage, and misrepair: implications for poor prognosis in AML, Blood, vol.111, issue.6, pp.3173-82, 2008.
DOI : 10.1182/blood-2007-05-092510

J. Hartmann, F. Braulke, U. Sinzig, G. Wulf, J. Maas et al., Iron overload impairs proliferation of erythroid progenitors cells (BFU-E) from patients with myelodysplastic syndromes. Leukemia research, pp.327-359, 2012.

K. Taoka, K. Kumano, F. Nakamura, M. Hosoi, S. Goyama et al., The effect of iron overload and chelation on erythroid differentiation, International Journal of Hematology, vol.25, issue.2, pp.149-59, 2011.
DOI : 10.1007/s12185-011-0988-3

H. Ghoti, E. Fibach, D. Merkel, G. Perez-avraham, S. Grisariu et al., Changes in parameters of oxidative stress and free iron biomarkers during treatment with deferasirox in ironoverloaded patients with myelodysplastic syndromes, Haematologica, vol.9528, issue.8, pp.1433-1437, 2010.

V. Pullarkat, A. Sehgal, L. Li, Z. Meng, A. Lin et al., Deferasirox exposure induces reactive oxygen species and reduces growth and viability of myelodysplastic hematopoietic progenitors. Leukemia research, pp.966-73, 2012.

C. Callens, S. Coulon, J. Naudin, I. Radford-weiss, N. Boissel et al., Targeting iron homeostasis induces cellular differentiation and synergizes with differentiating agents in acute myeloid leukemia. The Journal of experimental medicine, pp.731-5007, 2010.
URL : https://hal.archives-ouvertes.fr/hal-00473105

M. Roth, W. B. Simkin, G. Narayanagari, S. Barreyro, L. Bartholdy et al., Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation, Blood, vol.120, issue.2, pp.386-94, 2012.
DOI : 10.1182/blood-2011-12-399667

E. Paubelle, F. Zylbersztejn, S. Alkhaeir, F. Suarez, C. Callens et al., Deferasirox and Vitamin D Improves Overall Survival in Elderly Patients with Acute Myeloid Leukemia after Demethylating Agents Failure, PLoS ONE, vol.14, issue.6, p.65998, 2013.
DOI : 10.1371/journal.pone.0065998.t001

N. Mobilia, A. Donzé, J. Moulis, and F. E. , A Model of the Cellular Iron Homeostasis Network Using Semi-Formal Methods for Parameter Space Exploration, Electronic Proceedings in Theoretical Computer Science, vol.92, pp.42-57, 2012.
DOI : 10.4204/EPTCS.92.4

A. Donze, E. Fanchon, L. Gattepaille, O. Maler, and P. Tracqui, Robustness Analysis and Behavior Discrimination in Enzymatic Reaction Networks, PLoS ONE, vol.7, issue.9, p.2424608, 2011.
DOI : 10.1371/journal.pone.0024246.s002

URL : https://hal.archives-ouvertes.fr/hal-00846753

J. Goforth, S. Anderson, C. Nizzi, and R. Eisenstein, Multiple determinants within ironresponsive elements dictate iron regulatory protein binding and regulatory hierarchy, RNA, vol.1627, issue.111, pp.154-69, 2009.

B. Lozzio, C. Lozzio, E. Bamberger, and A. Feliu, A Multipotential Leukemia Cell Line (K-562) of Human Origin, Experimental Biology and Medicine, vol.166, issue.4, pp.546-5001, 1981.
DOI : 10.3181/00379727-166-41106

G. Kikuchi, T. Yoshida, and M. Noguchi, Heme oxygenase and heme degradation. Biochemical and biophysical research communications, pp.558-6724, 2005.

D. Haines, I. Lekli, P. Teissier, I. Bak, and A. Tosaki, Role of haeme oxygenase-1 in resolution of oxidative stress-related pathologies: focus on cardiovascular, lung, neurological and kidney disorders, Acta Physiologica, vol.46, issue.Suppl, pp.487-501, 2011.
DOI : 10.1111/j.1748-1716.2011.02387.x

T. Gimm, M. Wiese, B. Teschemacher, A. Deggerich, J. Schodel et al., Hypoxiainducible protein 2 is a novel lipid droplet protein and a specific target gene of hypoxia-inducible factor-1, FASEB journal : official publication of the Federation of American Societies for Experimental Biology, vol.2414, issue.11, pp.4443-5807, 2010.

S. Epsztejn, O. Kakhlon, H. Glickstein, W. Breuer, and I. Cabantchik, Fluorescence Analysis of the Labile Iron Pool of Mammalian Cells, Analytical Biochemistry, vol.248, issue.1, pp.31-4015, 1997.
DOI : 10.1006/abio.1997.2126

P. Chaudhary and V. Pullarkat, Deferasirox: appraisal of safety and efficacy in long-term therapy, Journal of blood medicine, vol.4, pp.101-111, 2013.

T. Chaston, R. Watts, J. Yuan, and D. Richardson, Potent antitumor activity of novel iron chelators derived from di-2-pyridylketone isonicotinoyl hydrazone involves fenton-derived free radical generation. Clinical cancer research : an official journal of the American Association for Cancer Research, pp.7365-74, 2004.