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Normal and malignant megakaryopoiesis

  • Qiang Wen (a1), Benjamin Goldenson (a1) and John D. Crispino (a1)
Abstract

Megakaryopoiesis is the process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal haemostasis. Over the past decade, molecular mechanisms that contribute to MK development and differentiation have begun to be elucidated. In this review, we provide an overview of megakaryopoiesis and summarise the latest developments in this field. Specially, we focus on polyploidisation, a unique form of the cell cycle that allows MKs to increase their DNA content, and the genes that regulate this process. In addition, because MKs have an important role in the pathogenesis of acute megakaryocytic leukaemia and a subset of myeloproliferative neoplasms, including essential thrombocythemia and primary myelofibrosis, we discuss the biology and genetics of these disorders. We anticipate that an increased understanding of normal MK differentiation will provide new insights into novel therapeutic approaches that will directly benefit patients.

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Corresponding author
*Corresponding author: John D. Crispino, Division of Hematology/Oncology, Northwestern University, 303 East Superior Street, Lurie 5-113, Chicago, IL 60611, USA. E-mail: j-crispino@northwestern.edu
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2 L. Kanz (1982) Identification of human megakaryocytes derived from pure megakaryocytic colonies (CFU-M), megakaryocytic-erythroid colonies (CFU-M/E), and mixed hemopoietic colonies (CFU-GEMM) by antibodies against platelet associated antigens. Blut 45, 267-274

3 T. Nakahata , A.J. Gross and M. Ogawa (1982) A stochastic model of self-renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture. Journal of Cellular Physiology 113, 455-458

4 K. Akashi (2000) A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193-197

5 T. Reya (2001) Stem cells, cancer, and cancer stem cells. Nature 414, 105-111

7 M. Kondo , I.L. Weissman and K. Akashi (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661-672

10 J. Adolfsson (2001) Upregulation of Flt3 expression within the bone marrow Lin(−)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 15, 659-669

11 J. Adolfsson (2005) Identification of Flt3+ lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121, 295-306

12 E.C. Forsberg (2006) New evidence supporting megakaryocyte-erythrocyte potential of flk2/flt3+ multipotent hematopoietic progenitors. Cell 126, 415-426

13 T.N. Nakorn , T. Miyamoto and I.L. Weissman (2003) Characterization of mouse clonogenic megakaryocyte progenitors. Proceedings of the National Academy of Sciences of the United States of America 100, 205-210

14 J. Tober (2007) The megakaryocyte lineage originates from hemangioblast precursors and is an integral component both of primitive and of definitive hematopoiesis. Blood 109, 1433-1441

15 J. Tober , K.E. McGrath and J. Palis (2008) Primitive erythropoiesis and megakaryopoiesis in the yolk sac are independent of c-myb. Blood 111, 2636-2639

16 X. Xie (2003) Thrombopoietin promotes mixed lineage and megakaryocytic colony-forming cell growth but inhibits primitive and definitive erythropoiesis in cells isolated from early murine yolk sacs. Blood 101, 1329-1335

18 L.A. Harker (1968) Kinetics of thrombopoiesis. Journal of Clinical Investigation 47, 458-465

20 L. Lordier (2008) Megakaryocyte endomitosis is a failure of late cytokinesis related to defects in the contractile ring and Rho/Rock signaling. Blood 112, 3164-3174

21 L. Lordier (2010) Aurora B is dispensable for megakaryocyte polyploidization, but contributes to the endomitotic process. Blood 116, 2345-2355

22 A. Eliades , N. Papadantonakis and K. Ravid (2010) New roles for cyclin E in megakaryocytic polyploidization. Journal of Biological Chemistry 285, 18909-18917

24 J.M. Zimmet (1997) A role for cyclin D3 in the endomitotic cell cycle. Molecular and Cellular Biology 17, 7248-7259

25 J.M. Zimmet , P. Toselli and K. Ravid (1998) Cyclin D3 and megakaryocyte development: exploration of a transgenic phenotype. Stem Cells 16 (Suppl. 2), 97-106

26 A.G. Muntean (2007) Cyclin D-Cdk4 is regulated by GATA-1 and required for megakaryocyte growth and polyploidization. Blood 109, 5199-5207

27 Y. Geng (2003) Cyclin E ablation in the mouse. Cell 114, 431-443

29 L. Gilles (2008) P19INK4D links endomitotic arrest and megakaryocyte maturation and is regulated by AML-1. Blood 111, 4081-4091

30 N.J. Ganem , Z. Storchova and D. Pellman (2007) Tetraploidy, aneuploidy and cancer. Current Opinion in Genetics and Development 17, 157-162

31 D. Ito and T. Matsumoto (2010) Molecular mechanisms and function of the spindle checkpoint, a guardian of the chromosome stability. Advances in Experimental Medicine and Biology 676, 15-26

32 T. Nakaya (2010) Critical role of Pcid2 in B cell survival through the regulation of MAD2 expression. Journal of Immunology 185, 5180-5187

33 P. Vernole (2009) TAp73alpha binds the kinetochore proteins Bub1 and Bub3 resulting in polyploidy. Cell Cycle 8, 421-429

34 Q. Wang (2004) BUBR1 deficiency results in abnormal megakaryopoiesis. Blood 103, 1278-1285

35 S. Ruchaud , M. Carmena and W.C. Earnshaw (2007) Chromosomal passengers: conducting cell division. Nature Reviews. Molecular Cell Biology 8, 798-812

36 S. Gurbuxani (2005) Differential requirements for survivin in hematopoietic cell development. Proceedings of the National Academy of Sciences of the United States of America 102, 11480-11485

37 Q. Wen (2009) Survivin is not required for the endomitotic cell cycle of megakaryocytes. Blood 114, 153-156

38 A.E. Geddis and K. Kaushansky (2004) Megakaryocytes express functional Aurora-B kinase in endomitosis. Blood 104, 1017-1024

39 Y. Zhang (2004) Aberrant quantity and localization of Aurora-B/AIM-1 and survivin during megakaryocyte polyploidization and the consequences of Aurora-B/AIM-1-deregulated expression. Blood 103, 3717-3726

40 F.A. Barr and U. Gruneberg (2007) Cytokinesis: placing and making the final cut. Cell 131, 847-860

41 M.E. Burkard (2007) Chemical genetics reveals the requirement for Polo-like kinase 1 activity in positioning RhoA and triggering cytokinesis in human cells. Proceedings of the National Academy of Sciences of the United States of America 104, 4383-4388

42 D.M. Lowery (2007) Proteomic screen defines the Polo-box domain interactome and identifies Rock2 as a Plk1 substrate. EMBO Journal 26, 2262-2273

43 M. Petronczki (2007) Polo-like kinase 1 triggers the initiation of cytokinesis in human cells by promoting recruitment of the RhoGEF Ect2 to the central spindle. Developmental Cell 12, 713-725

44 M. Yagi and G.J. Roth (2006) Megakaryocyte polyploidization is associated with decreased expression of polo-like kinase (PLK). Journal of Thrombosis and Haemostasis 4, 2028-2034

45 A.B. Cantor and S.H. Orkin (2002) Transcriptional regulation of erythropoiesis: an affair involving multiple partners. Oncogene 21, 3368-3376

46 R.A. Shivdasani (1997) A lineage-selective knockout establishes the critical role of transcription factor GATA-1 in megakaryocyte growth and platelet development. EMBO Journal 16, 3965-3973

48 A.P. Tsang (1998) Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG. Genes and Development 12, 1176-1188

49 A.N. Chang (2002) GATA-factor dependence of the multitype zinc-finger protein FOG-1 for its essential role in megakaryopoiesis. Proceedings of the National Academy of Sciences of the United States of America 99, 9237-9242

50 J.D. Crispino (2005) GATA1 in normal and malignant hematopoiesis. Seminars in Cell and Developmental Biology 16, 137-147

51 V.N. Tubman (2007) X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation. Blood 109, 3297-3299

52 J.D. Phillips (2007) Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria. Blood 109, 2618-2621

53 A. Miccio (2010) NuRD mediates activating and repressive functions of GATA-1 and FOG-1 during blood development. EMBO Journal 29, 442-456

54 G.D. Gregory (2010) FOG1 requires NuRD to promote hematopoiesis and maintain lineage fidelity within the megakaryocytic-erythroid compartment. Blood 115, 2156-2166

55 W.D. Tracey and N.A. Speck (2000) Potential roles for RUNX1 and its orthologs in determining hematopoietic cell fate. Seminars in Cell and Developmental Biology 11, 337-342

56 M. Kundu (2002) Role of Cbfb in hematopoiesis and perturbations resulting from expression of the leukemogenic fusion gene Cbfb-MYH11. Blood 100, 2449-2456

57 K.E. Elagib (2003) RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood 101, 4333-4341

58 R.B. Lorsbach (2004) Role of RUNX1 in adult hematopoiesis: analysis of RUNX1-IRES-GFP knock-in mice reveals differential lineage expression. Blood 103, 2522-2529

59 M. Ichikawa (2004) AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nature Medicine 10, 299-304

60 J.D. Growney (2005) Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood 106, 494-504

61 G. Putz (2006) AML1 deletion in adult mice causes splenomegaly and lymphomas. Oncogene 25, 929-939

62 W. Sun and J.R. Downing (2004) Haploinsufficiency of AML1 results in a decrease in the number of LTR-HSCs while simultaneously inducing an increase in more mature progenitors. Blood 104, 3565-3572

65 L.F. Peterson and D.E. Zhang (2004) The 8;21 translocation in leukemogenesis. Oncogene 23, 4255-4262

66 H. Hock (2004) Tel/Etv6 is an essential and selective regulator of adult hematopoietic stem cell survival. Genes and Development 18, 2336-2341

67 A. Hart (2000) Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia. Immunity 13, 167-177

68 D.D. Spyropoulos (2000) Hemorrhage, impaired hematopoiesis, and lethality in mouse embryos carrying a targeted disruption of the Fli1 transcription factor. Molecular and Cellular Biology 20, 5643-5652

69 S. Ano (2004) Erythroblast transformation by FLI-1 depends upon its specific DNA binding and transcriptional activation properties. Journal of Biological Chemistry 279, 2993-3002

70 M. Athanasiou (2000) FLI-1 is a suppressor of erythroid differentiation in human hematopoietic cells. Leukemia 14, 439-445

71 L. Pang (2006) Maturation stage-specific regulation of megakaryopoiesis by pointed-domain Ets proteins. Blood 108, 2198-2206

72 M.J. Stankiewicz and J.D. Crispino (2009) ETS2 and ERG promote megakaryopoiesis and synergize with alterations in GATA-1 to immortalize hematopoietic progenitor cells. Blood 113, 3337-3347

73 S. Salek-Ardakani (2009) ERG is a megakaryocytic oncogene. Cancer Research 69, 4665-4673

74 M.A. Hall (2003) The critical regulator of embryonic hematopoiesis, SCL, is vital in the adult for megakaryopoiesis, erythropoiesis, and lineage choice in CFU-S12. Proceedings of the National Academy of Sciences of the United States of America 100, 992-997

75 T. Tripic (2009) SCL and associated proteins distinguish active from repressive GATA transcription factor complexes. Blood 113, 2191-2201

76 C. Gekas (2009) Mef2C is a lineage-restricted target of Scl/Tal1 and regulates megakaryopoiesis and B-cell homeostasis. Blood 113, 3461-3471

77 Z. Ma (2001) Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nature Genetics 28, 220-221

78 S. Halene (2010) Serum response factor is an essential transcription factor in megakaryocytic maturation. Blood 116, 1942-1950

79 C. Ragu (2010) The serum response factor (SRF)/megakaryocytic acute leukemia (MAL) network participates in megakaryocyte development. Leukemia 24, 1227-1230

81 P.J. Fialkow , S.M. Gartler and A. Yoshida (1967) Clonal origin of chronic myelocytic leukemia in man. Proceedings of the National Academy of Sciences of the United States of America 58, 1468-1471

82 D.G. Gilliland (1991) Clonality in myeloproliferative disorders: analysis by means of the polymerase chain reaction. Proceedings of the National Academy of Sciences of the United States of America 88, 6848-6852

83 J.W. Adamson (1976) Polycythemia vera: stem-cell and probable clonal origin of the disease. New England Journal of Medicine 295, 913-916

84 A. Tefferi (2000) Myelofibrosis with myeloid metaplasia. New England Journal of Medicine 342, 1255-1265

85 E.J. Baxter (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365, 1054-1061

86 C. James (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434, 1144-1148

87 R. Kralovics (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. New England Journal of Medicine 352, 1779-1790

88 R.L. Levine (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7, 387-397

89 P. Saharinen , K. Takaluoma and O. Silvennoinen (2000) Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Molecular and Cellular Biology 20, 3387-3395

90 J.N. Ihle and D.G. Gilliland (2007) Jak2: normal function and role in hematopoietic disorders. Current Opinion in Genetics and Development 17, 8-14

91 L.M. Scott (2006) Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia. Blood 108, 2435-2437

92 L.M. Scott (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. New England Journal of Medicine 356, 459-468

93 G. Wernig (2006) Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 107, 4274-4281

94 R. Tiedt (2008) Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood 111, 3931-3940

95 C. Lacout (2006) JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 108, 1652-1660

96 Z. Huang (2007) STAT1 promotes megakaryopoiesis downstream of GATA-1 in mice. Journal of Clinical Investigation 117, 3890-3899

98 M.A. Dawson (2009) JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 461, 819-822

99 D.S. Griffiths (2011) LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease. Nature Cell Biology 13, 13-21

100 H. Akada (2010) Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera-like disease. Blood 115, 3589-3597

101 J. Li (2010) JAK2 V617F impairs hematopoietic stem cell function in a conditional knock-in mouse model of JAK2 V617F-positive essential thrombocythemia. Blood 116, 1528-1538

102 C. Marty (2010) Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. Blood 116, 783-787

103 A. Mullally (2010) Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 17, 584-596

104 Y. Pikman (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Medicine 3, e270

105 R. Chaligne (2008) New mutations of MPL in primitive myelofibrosis: only the MPL W515 mutations promote a G1/S-phase transition. Leukemia 22, 1557-1566

106 A.D. Pardanani (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108, 3472-3476

107 P.A. Beer (2008) MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 112, 141-149

108 J. Ding (2004) Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 103, 4198-4200

109 A.M. Vannucchi (2008) Characteristics and clinical correlates of MPL 515W > L/K mutation in essential thrombocythemia. Blood 112, 844-847

110 P. Guglielmelli (2007) Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. British Journal of Haematology 137, 244-247

111 S. Takaki (2002) Enhanced hematopoiesis by hematopoietic progenitor cells lacking intracellular adaptor protein, Lnk. Journal of Experimental Medicine 195, 151-160

112 W. Tong and H.F. Lodish (2004) Lnk inhibits Tpo-mpl signaling and Tpo-mediated megakaryocytopoiesis. Journal of Experimental Medicine 200, 569-580

113 L. Velazquez (2002) Cytokine signaling and hematopoietic homeostasis are disrupted in Lnk-deficient mice. Journal of Experimental Medicine 195, 1599-1611

114 T.L. Lasho , A. Pardanani and A. Tefferi (2010) LNK mutations in JAK2 mutation-negative erythrocytosis. New England Journal of Medicine 363, 1189-1190

115 S.T. Oh (2010) Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 116, 988-992

116 A. Pardanani (2010) LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 24, 1713-1718

117 T.L. Lasho (2011) Clonal hierarchy and allelic mutation segregation in a myelofibrosis patient with two distinct LNK mutations. Leukemia 25, 1056-8

119 A. Bersenev (2010) Lnk constrains myeloproliferative diseases in mice. Journal of Clinical Investigation 120, 2058-2069

120 F. Delhommeau (2009) Mutation in TET2 in myeloid cancers. New England Journal of Medicine 360, 2289-2301

121 N. Carbuccia (2009) Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 23, 2183-2186

122 A. Green and P. Beer (2010) Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. New England Journal of Medicine 362, 369-370

123 A. Tefferi (2010) IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 24, 1302-1309

124 F.H. Grand (2009) Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 113, 6182-6192

125 R. Jager (2010) Deletions of the transcription factor Ikaros in myeloproliferative neoplasms. Leukemia 24, 1290-1298

126 T. Ernst (2010) Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nature Genetics 42, 722-726

127 A. Tefferi and W. Vainchenker (2011) Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. Journal of Clinical Oncology 29, 573-582

130 S. Marubayashi (2010) HSP90 is a therapeutic target in JAK2-dependent myeloproliferative neoplasms in mice and humans. Journal of Clinical Investigation 120, 3578-3593

131 Y. Wang (2009) Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells. Blood 114, 5024-5033

132 P. Guglielmelli (2011) Safety and efficacy of everolimus, a mTOR inhibitor, as single agent in a phase 1/2 study in patients with myelofibrosis. Blood 118, 2069-2076

134 L. Pagano (2002) Acute megakaryoblastic leukemia: experience of GIMEMA trials. Leukemia 16, 1622-1626

135 D.R. Barnard (2007) Comparison of childhood myelodysplastic syndrome, AML FAB M6 or M7, CCG 2891: report from the Children's Oncology Group. Pediatric Blood and Cancer 49, 17-22

136 H. Hasle (2008) Myeloid leukemia in children 4 years or older with Down syndrome often lacks GATA1 mutation and cytogenetics and risk of relapse are more akin to sporadic AML. Leukemia 22, 1428-1430

137 C. Langebrake , U. Creutzig and D. Reinhardt (2005) Immunophenotype of Down syndrome acute myeloid leukemia and transient myeloproliferative disease differs significantly from other diseases with morphologically identical or similar blasts. Klinische Padiatrie 217, 126-134

138 U. Creutzig (2005) AML patients with Down syndrome have a high cure rate with AML-BFM therapy with reduced dose intensity. Leukemia 19, 1355-1360

139 A. Rao (2006) Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials. British Journal of Haematology 132, 576-583

140 A.S. Gamis (2003) Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children's Cancer Group Study 2891. Journal of Clinical Oncology 21, 3415-3422

141 C.M. Zwaan (2002) Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood 99, 245-251

142 A.S. Gamis (2005) Acute myeloid leukemia and Down syndrome evolution of modern therapy – -state of the art review. Pediatric Blood and Cancer 44, 13-20

143 A. Wickrema and J.D. Crispino (2007) Erythroid and megakaryocytic transformation. Oncogene 26, 6803-6815

144 P. Vyas and J.D. Crispino (2007) Molecular insights into Down syndrome-associated leukemia. Current Opinion in Pediatrics 19, 9-14

145 L.M. Hollanda (2006) An inherited mutation leading to production of only the short isoform of GATA-1 is associated with impaired erythropoiesis. Nature Genetics 38, 807-812

146 Z. Li (2005) Developmental stage-selective effect of somatically mutated leukemogenic transcription factor GATA1. Nature Genetics 37, 613-619

147 S. Malinge , S. Izraeli and J.D. Crispino (2009) Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood 113, 2619-2628

148 D.K. Walters (2006) Activating alleles of JAK3 in acute megakaryoblastic leukemia. Cancer Cell 10, 65-75

149 H. Kiyoi (2007) JAK3 mutations occur in acute megakaryoblastic leukemia both in Down syndrome children and non-Down syndrome adults. Leukemia 21, 574-576

150 S. De Vita (2007) Loss-of-function JAK3 mutations in TMD and AMKL of Down syndrome. British Journal of Haematology 137, 337-341

151 T. Sato (2008) Functional analysis of JAK3 mutations in transient myeloproliferative disorder and acute megakaryoblastic leukaemia accompanying Down syndrome. British Journal of Haematology 141, 681-688

152 M.G. Cornejo , T.J. Boggon and T. Mercher (2009) JAK3: a two-faced player in hematological disorders. International Journal of Biochemistry and Cell Biology 41, 2376-2379

153 I. Radtke (2009) Genomic analysis reveals few genetic alterations in pediatric acute myeloid leukemia. Proceedings of the National Academy of Sciences of the United States of America 106, 12944-12949

154 S. Leow (2011) FLT3 mutation and expression did not adversely affect clinical outcome of childhood acute leukaemia-a study of 531 Southeast Asian children by the Ma-Spore study group. Hematological Oncology doi: 10.1002/hon.987. [Epub ahead of print]

155 J.H. Klusmann (2010) Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis. Genes and Development 24, 1659-1672

156 Y. Ge (2006) Differential gene expression, GATA1 target genes, and the chemotherapy sensitivity of Down syndrome megakaryocytic leukemia. Blood 107, 1570-1581

157 J.P. Bourquin (2006) Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proceedings of the National Academy of Sciences of the United States of America 103, 3339-3344

159 J. Bernstein (2000) Nineteen cases of the t(1;22)(p13;q13) acute megakaryblastic leukaemia of infants/children and a review of 39 cases: report from a t(1;22) study group. Leukemia 14, 216-218

160 J.E. Rubnitz (2007) Prognostic factors and outcome of recurrence in childhood acute myeloid leukemia. Cancer 109, 157-163

161 T. Mercher (2001) Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proceedings of the National Academy of Sciences of the United States of America 98, 5776-5779

162 F. Miralles (2003) Actin dynamics control SRF activity by regulation of its coactivator MAL. Cell 113, 329-342

163 A. Descot (2008) OTT-MAL is a deregulated activator of serum response factor-dependent gene expression. Molecular and Cellular Biology 28, 6171-6181

164 M. Ariyoshi and J.W. Schwabe (2003) A conserved structural motif reveals the essential transcriptional repression function of Spen proteins and their role in developmental signaling. Genes and Development 17, 1909-1920

165 F. Oswald (2002) SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO Journal 21, 5417-5426

166 X. Ma (2007) Rbm15 modulates notch-induced transcriptional activation and affects myeloid differentiation. Molecular and Cellular Biology 27, 3056-3064

168 M. Abdelhaleem (2007) High incidence of CALM-AF10 fusion and the identification of a novel fusion transcript in acute megakaryoblastic leukemia in children without Down's syndrome. Leukemia 21, 352-353

169 Y. Oki (2006) Adult acute megakaryocytic leukemia: an analysis of 37 patients treated at M.D. Anderson Cancer Center. Blood 107, 880-884

S. Verstovsek (2010) Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clinical Cancer Research 16, 1988-1996

A. Pardanani (2011) JAK inhibitor therapy for myelofibrosis: critical assessment of value and limitations. Leukemia 25, 218-225

E. Chen (2010) Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell 18, 524-535

H. Chagraoui (2011) SCL-mediated regulation of the cell-cycle regulator p21 is critical for murine megakaryopoiesis. Blood 118, 723-735.

L. Doré and J.D. Crispino (2011) Transcription factor networks in erythroid cell and megakaryocyte development. Blood 118, 231-239

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