Comparison of mutated ABL1 and JAK2 as oncogenes and drug targets in myeloproliferative disorders

Leukemia

Volumn 22, Issue 7, 2008, Pages 1320-1334

  Walz, C ^a   Cross, N C P ^b   Van Etten, R A ^a   Reiter, A ^c  

^a TUFTS MEDICAL CENTER   (United States)

^b UNIVERSITY OF SOUTHAMPTON   (United Kingdom)

^c UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

12 (2 CYANOETHYL) 6,7,12,13 TETRAHYDRO 13 METHYL 5 OXOINDOLO[2,3 A]PYRROLO[3,4 C]CARBAZOLE; 4 (3 DIMETHYLAMINO 1 PYRROLIDINYLMETHYL) 3 TRIFLUOROMETHYL N [4 METHYL 3 [[4 (5 PYRIMIDINYL) 2 PYRIMIDINYL]AMINO]PHENYL]BENZAMIDE; ABELSON KINASE; ABELSON KINASE 1; ANTINEOPLASTIC AGENT; AT 9283; AURORA KINASE INHIBITOR; AZ 60; AZD 1480; BCR ABL PROTEIN; BOSUTINIB; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; CYTARABINE; DASATINIB; HISTONE DEACETYLASE INHIBITOR; IMATINIB; INCBO 18424; INTERFERON; ITF 2357; JANUS KINASE 2; LESTAURTINIB; LS 104; NILOTINIB; PHOSPHOTRANSFERASE INHIBITOR; PROTEIN TYROSINE KINASE; SB 1518; TG 101209; TG 101348; XL 019;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOCYTIC LEUKEMIA; ALLOGENEIC STEM CELL TRANSPLANTATION; ANTINEOPLASTIC ACTIVITY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG DOSE INCREASE; DRUG DOSE REGIMEN; DRUG SUBSTITUTION; DRUG SYNTHESIS; DRUG TARGETING; DRUG WITHDRAWAL; GENE DELETION; GENE INSERTION; HUMAN; IC 50; LYMPHOMA; MALIGNANT TRANSFORMATION; MULTIPLE MYELOMA; MYELOID METAPLASIA; MYELOPROLIFERATIVE DISORDER; NEUTROPENIA; NONHUMAN; ONCOGENE; PATHOGENESIS; PHENOTYPE; PLEURA EFFUSION; POINT MUTATION; PRIORITY JOURNAL; PROTEIN FUNCTION; RECIPROCAL CHROMOSOME TRANSLOCATION; REVIEW; THROMBOCYTOPENIA;

ANIMALS; AUTOANTIGENS; CELL CYCLE PROTEINS; GENES, ABL; HUMANS; JANUS KINASE 2; MUTATION; MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA VERA; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-ABL;

EID: 47649127591     PISSN: 08876924     EISSN: 14765551     Source Type: Journal    
DOI: 10.1038/leu.2008.133     Document Type: Review

References (198)

1. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951; 6: 372-375.
2. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002; 100: 2292-2302.
3. Tefferi A. The history of myeloproliferative disorders: Before and after Dameshek. Leukemia 2008; 22: 3-13.
4. Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960; 25: 85-109.
5. Rowley JD. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973; 243: 290-293.
6. Daley GQ, Van Etten RA, Baltimore D. Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 1990; 247: 824-830.
7. Daley GQ, Van Etten RA, Baltimore D. Blast crisis in a murine model of chronic myelogenous leukemia. Proc Natl Acad Sci USA 1991; 88 11335-11338.
8. Ben-Neriah Y, Daley GQ, Mes-Masson AM, Witte ON, Baltimore D. The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. Science 1986; 233: 212-214.
9. McLaughlin J, Chianese E, Witte ON. In vitro transformation of immature hematopoietic cells by the P210 BCR/ABL oncogene product of the Philadelphia chromosome. Proc Natl Acad Sci USA 1987; 84: 6558-6562.
10. Reiter A, Walz C, Cross NCP. Tyrosine kinases as therapeutic targets in BCR-ABL negative chronic myeloproliferative disorders. Curr Drug Targets 2007; 8: 205-216.
11. Vizmanos JL, Hernandez R, Vidal MJ, Larrayoz MJ, Odero MD, Marin J et al. Clinical variability of patients with the t(6;8)(q27;p12) and FGFR1OP-FGFR1 fusion: Two further cases. Hematol J 2004; 5: 534-537.
12. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144-1148.
13. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352: 1779-1790.
14. Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ et al Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 2005; 7: 387-397.
15. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365: 1054-1061.
16. Zhao R, Xing S, Li Z, Fu X, Li Q, Krantz SB et al. Identification of an acquired JAK2 mutation in Polycythemia vera. J Biol Chem 2005; 280: 22788-22792.
17. Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356: 459-468.
18. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472-3476.
19. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: E270.
20. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005; 353: 172-187.
21. Wetzler M, Talpaz M, Van Etten RA, Hirsh-Ginsberg C, Beran M, Kurzrock R. Subcellular localization of Bcr, Abl, and Bcr-Abl proteins in normal and leukemic cells and correlation of expression with myeloid differentiation. J Clin Invest 1993; 92: 1925-1939.
22. Behrmann I, Smyczek T, Heinrich PC, Schmitz-Van de LH, Komyod W, Giese B et al. Janus kinase (Jak) subcellular localization revisited: The exclusive membrane localization of endogenous Janus kinase 1 by cytokine receptor interaction uncovers the Jak.receptor complex to be equivalent to a receptor tyrosine kinase. J Biol Chem 2004; 279: 35486-35493.
23. Lobie PE, Ronsin B, Silvennoinen O, Haldosen LA, Norstedt G, Morel G. Constitutive nuclear localization of Janus kinases 1 and 2. Endocrinology 1996; 137: 4037-4045.
24. Wen ST, Jackson PK, Van Etten RA. The cytostatic function of c-AbI is controlled by multiple nuclear localization signals and requires the p53 and Rb tumor suppressor gene products. EMBO J 1996; 15: 1583-1595.
25. Taagepera S, McDonald D, Loeb JE, Whitaker LL, McElroy AK, Wang JY et al. Nuclear-cytoplasmic shuttling of C-ABL tyrosine kinase. Proc Natl Acad Sci USA 1998; 95: 7457-7462.
26. Van Etten RA. Cycling, stressed-out and nervous: Cellular functions of c-Abl. Trends Cell Biol 1999; 9: 179-186.
27. Yoshida K, Miki Y. Enabling death by the AbI tyrosine kinase: Mechanisms for nuclear shuttling of c-AbI in response to DNA damage. Cell Cycle 2005; 4: 777-779.
28. Yoshida K. Regulation for nuclear targeting of the AbI tyrosine kinase in response to DNA damage. Adv Exp Med Biol 2007; 604: 155-165.
29. Wen ST, Van Etten RA. The PAG gene product, a stress-induced protein with antioxidant properties, is an Abl SH3-binding protein and a physiological inhibitor of c-AbI tyrosine kinase activity. Genes Dev 1997; 11: 2456-2467.
30. Welch PJ, Wang JY. Abrogation of retinoblastoma protein function by c-Abl through tyrosine kinase-dependent and -independent mechanisms. Mol Cell Biol 1995; 15: 5542-5551.
31. Sawyers CL, McLaughlin J, Goga A, Havlik M, Witte O. The nuclear tyrosine kinase c-Abl negatively regulates cell growth. Cell 1994; 77: 121-131.
32. Wang JY. Abl tyrosine kinase in signal transduction and cell-cycle regulation. Curr Opin Genet Dev 1993; 3: 35-43.
33. Schwartzberg PL, Stall AM, Hardin JD, Bowdish KS, Humaran T, Boast S et al. Mice homozygous for the ablml mutation show poor viability and depletion of selected B and T cell populations. Cell 1991; 65 1165-1175.
34. Kharbanda S, Pandey P, Morris PL, Whang Y, Xu Y, Sawant S et al. Functional role for the c-Abl tyrosine kinase in meiosis I. Oncogene 1998; 16: 1773-1777.
35. Tybulewicz VL, Crawford CE, Jackson PK, Bronson RT, Mulligan RC. Neonatal lethality and lymphopenia in mice with a homozygous disruption of the c-abl proto-oncogene. Cell 1991; 65: 1153-1163.
36. Ching YP, Qi Z, Wang JH. Cloning of three novel neuronal Cdk5 activator binding proteins. Gene 2000; 242: 285-294.
37. Hardin JD, Boast S, Schwartzberg PL, Lee G, Alt FW, Stall AM et al Bone marrow B lymphocyte development in c-abl-deficient mice. Cell Immunol 1995; 165: 44-54.
38. Hardin JD, Boast S, Schwartzberg PL, Lee G, Alt FW, Stall AM et al Abnormal peripheral lymphocyte function in c-abl mutant mice. Cell Immunol 1996; 172: 100-107.
39. Nagar B, Hantschel O, Young MA, Scheffzek K, Veach D, Bornmann V et al. Structural basis for the autoinhibition of c-Abl tyrosine kinase. Cell 2003; 112: 859-871.
40. Pluk H, Dorey K, Superti-Furga G. Autoinhibition of c-Abl. Cell 2002; 108: 247-259.
41. Van Etten RA. c-Abl regulation: A tail of two lipids. Curr Biol 2003; 13: R608-R610.
42. Plattner R, Irvin BJ, Guo S, Blackburn K, Kazlauskas A, Abraham RT et al. A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1. Nat Cell Biol 2003; 5: 309-319.
43. Arlinghaus RB. Bcr: A negative regulator of the Bcr-Abl oncoprotein in leukemia. Oncogene 2002; 21: 8560-8567.
44. Saharinen P, Takaluoma K, Silvennoinen O. Regulation of the Jak2 tyrosine kinase by its pseudokinase domain. Mol Cell Biol 2000; 20: 3387-3395.
45. Ma AC, Ward AC, Liang R, Leung AY. The role of jak2a in zebrafish hematopoiesis. Blood 2007; 110: 1824-1830.
46. Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell 1998; 93: 385-395.
47. Funakoshi-Tago M, Pelletier S, Matsuda T, Parganas E, Ihle JN. Receptor specific downregulation of cytokine signaling by autophosphorylation in the FERM domain of Jak2. EMBO J 2006; 25: 4763-4772.
48. Kazansky AV, Kabotyanski EB, Wyszomierski SL, Mancini MA, Rosen JM. Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A. J Biol Chem 1999; 274: 22484-22492.
49. Meyer T, Vinkemeier U. STAT nuclear translocation: Potential for pharmacological intervention. Expert Opin Ther Targets 2007; 11 1355-1365.
50. Ilaria Jr RL, Van Etten RA. P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members. J Biol Chem 1996; 271: 31704-31710.
51. Xie S, Wang Y, Liu J, Sun T, Wilson MB, Smithgall TE et al. Involvement of Jak2 tyrosine phosphorylation in Bcr-Abl transformation. Oncogene 2001; 20: 6188-6195.
52. Samanta AK, Lin H, Sun T, Kantarjian H, Arlinghaus RB. Janus kinase 2: A critical target in chronic myelogenous leukemia. Cancer Res 2006; 66: 6468-6472.
53. Wernig G, Mercher T, Okabe R, Levine RL, Lee BH, Gilliland DG. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 2006; 107: 4274-4281.
54. Schwaller J, Frantsve J, Aster J, Williams IR, Tomasson MH, Ross TS et al. Transformation of hematopoietic cell lines to growth-factor independence and induction of a fatal myelo- and lymphoproliferative disease in mice by retrovirally transduced TEL/JAK2 fusion genes. EMBO J 1998; 17: 5321-5333.
55. Schwaller J, Parganas E, Wang D, Cain D, Aster JC, Williams IR et al Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Mol Cell 2000; 6: 693-704.
56. Barnes DJ, Melo JV. Cytogenetic and molecular genetic aspects of chronic myeloid leukaemia. Acta Haematol 2002; 108: 180-202.
57. Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R et al Neutrophilic-chronic myeloid leukemia: A distinct disease with a specific molecular marker (BCR/ABL with C3/A2 junction). Blood 1996; 88: 2410-2414.
58. Calabretta B, Perrotti D. The biology of CML blast crisis. Blood 2004; 103: 4010-4022.
59. Klejman A, Schreiner SJ, Nieborowska-Skorska M, Slupianek A, Wilson M, Smithgall TE et al. The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cells. EMBO J 2002; 21: 5766-5774.
60. Xie S, Lin H, Sun T, Arlinghaus RB. Jak2 is involved in c-Myc induction by Bcr-Abl. Oncogene 2002; 21: 7137-7146.
61. Nosaka T, Kawashima T, Misawa K, Ikuta K, Mui AL, Kitamura T. STAT5 as a molecular regulator 4 proliferation, differentiation and apoptosis in hematopoietic cells. EMBO J 1999; 18: 4754-4765.
62. Sattler M, Mohi MG, Pride YB, Quinnan LR, Malouf NA, Podar K et al Critical role for Gab2 in transformation by BCR/ABL. Cancer Cell 2002; 1: 479-492.
63. Neviani P, Santhanam R, Trotta R, Notari M, Blaser BW, Liu S et al The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein. Cancer Cell 2005; 8: 355-368.
64. Graux C, Cools J, Melotte C, Quentmeier H, Ferrando A, Levine R et al Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia. Nat Genet 2004; 36: 1084-1089.
65. Burmeister T, Gokbuget N, Reinhardt R, Rieder H, Hoelzer D, Schwartz S. NUP214-ABL1 in adult T-ALL: The GMALL study group experience. Blood 2006; 108: 5556-3559.
66. De Keersmaecker K, Graux C, Odero MD, Mentens N, Somers R, Maertens J et al. Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32). Blood 2005; 105: 4849-4852.
67. Andreasson P, Johansson B, Carlsson M, Jarlsfelt I, Fioretos T, Mitelman F et al. BCR/ABL-negative chronic myeloid leukemia with ETV6/ABL fusion. Genes Chromosomes Cancer 1997; 20: 299-304.
68. Million RP, Aster J, Gilliland DG, Van Etten RA. The Tel-Abl (ETV6-Abl) tyrosine kinase, product of complex (9;12) translocations in human leukemia, induces distinct myeloproliferative disease in mice. Blood 2002; 99: 4568-4577.
69. Soler G, Radford-Weiss J, Ben-Abdelali R, Mahlaoui N, Ponceau JF, Macintyre EA et al. Fusion of ZMIZ1 to ABL1 in a B-cell acute lymphoblastic leukaemia with a t(9;10)(q34;q22.3) translocation. Leukemia 2008; (in press).
70. De Braekeleer E, Douet-Guilbert N, Le Bris MJ, Berthou C, Morel F, De BM. A new partner gene fused to ABIL1 in a t(1;9)(q24;q34)-associated B-cell acute lymphoblastic leukemia. Leukemia 2007; 21: 2220-2221.
71. Heisterkamp N, Stephenson JR, Groffen J, Hansen PF, de Klein A, Bartram CR et al. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature 1983; 306: 239-242.
72. Reiter A, Walz C, Watmore A, Schoch C, Blau J, Schlegelberger B et al The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer Res 2005; 65: 2662-2667.
73. Corvi R, Berger N, Balczon R, Romeo G. RET/PCM-1: A novel fusion gene in papillary thyroid carcinoma. Oncogene 2000; 19: 4236-4242.
74. Bousquet M, Quelen C, De MV, Duchayne E, Roquefeuil B, Delsol G et al The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. Oncogene 2005; 24 7248-7252.
75. Murati A, Gelsi-Boyer V, Adelaide J, Perot C, Talmant P, Giraudier S et al. PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia 2005; 19 1692-1696.
76. Heiss S, Erdel M, Gunsilius E, Nachbaur D, Tzankov A. Myelodysplastic/ myeloproliferative disease with erythropoietic hyperplasia (erythroid preleukemia) and the unique translocation (8;9)(p23;p24): First description of a case. Hum Pathol 2005; 36: 1148-1151.
77. Adelaide J, Perot C, Gelsi-Boyer V, Pautas C, Murati A, Copie-Bergman C et al. A t(8;9) translocation with PCM1-JAK2 fusion a patient with T-cell lymphoma. Leukemia 2006; 20: 536-537.
78. Jones AV, Cross NC. Oncogenic derivatives of platelet-derived growth factor receptors. Cell Mol Life Sci 2004; 61: 2912-2923.
79. Griesinger F, Podleschny M, Steffens R, Bohlander S, Woermann B, Haase D. A novel BCR-JAK2 fusion gene is the result of a translocation (9;22)(p24;q11) in a case of CML. Blood 2000; 96: 352a.
80. Peeters P, Raynaud SD, Cools J, Wlodarska I, Grosgeorge J, Philip P et al. Fusion of TEL, the ETS-variant gene 6 (ETV6) to the receptor-associated kinase JAK2 as a result of t(9,12) in a lymphoid and t(9;15;12) in a myeloid leukemia. Blood 1997; 90: 2535-2540.
81. Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001; 293: 876-880.
82. Hochhaus A, Kreil S, Corbin AS, La Rosee P, Muller MC, Lahaye T et al Molecular and chromosomal mechanisms of resistance to imatinib (ST1571) therapy. Leukemia 2002; 16: 2190-2196.
83. Shah NP, Nicoll JM, Nagar B, Gorre ME, Paquette RL, Kuriyan J et al Multiple BCR-ABL kinase domain mutations confer polyclonal resistance to the tyrosine kinase inhibitor imatinib (STI1571) in chronic phase and blast crisis chronic myeloid leukemia. Cancer Cell 2002; 2: 117-125.
84. Branford S, Rudzki Z, Walsh S, Grigg A, Arthur C, Taylor K et al. High frequency of point mutations clustered within the adenosine triphosphate-binding region of BCR/ABL in patients with chronic myeloid leukemia or Ph-positive acute lymphoblastic leukemia who develop imatinib (STI571) resistance. Blood 2002; 99: 3472-3475.
85. Branford S, Rudzki Z, Walsh S, Parkinson I, Grigg A, Szer J et al. Detection of BCR-ABL mutations in patients with CML treated with imatinib is virtually always accompanied by clinical resistance, and mutations in the ATP phosphate-binding loop (P-loop) are associated with a poor prognosis. Blood 2003; 102: 276-283.
86. Apperley JF. Part I: Mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007; 8: 1018-1029
87. Apperley JF. Part II: Management of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007; 8: 1116-1128.
88. Soverini S, Martinelli G, Rosti G, Bassi S, Amabile M, Poerio A et al ABL mutations in late chronic phase chronic myeloid leukemia patients with up-front cytogenetic resistance to imatinib are associated with a greater likelihood of progression to blast crisis and shorter survival: A study by the GIMEMA Working Party on Chronic Myeloid Leukemia. J Clin Oncol 2005; 23: 4100-4109.
89. Soverini S, Colarossi S, Gnani A, Rosti G, Castagnetti F, Poerio A et al. Contribution of ABL kinase domain mutations to imatinib resistance in different subsets of Philadelphia-positive patients: By the GIMEMA Working Party on Chronic Myeloid Leukemia. Clin Cancer Res 2006; 12: 7374-7379.
90. Dupont S, Masse A, James C, Teyssandier I, Lecluse Y, Larbret F et al The JAK2 617V>F mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera. Blood 2007; 110: 1013-1021.
91. Tao WJ, Lin H, Sun T, Samanta AK, Arlinghaus R. BCR-ABL oncogenic transformation of NIH 3T3 fibroblasts requires the IL-3 receptor. Oncogene 2008; 27: 3194-3200.
92. Lu X, Huang LJ, Lodish HF. Dimerization by a cytokine receptor is necessary for constitutive activation of JAK2V617F. J Biol Chem 2008; 283: 5258-5266.
93. Zaleskas VM, Krause DS, Lazarides K, Patel N, Hu Y, Li S et al. Molecular pathogenesis and therapy of polycythemia induced in mice by JAK2 V617F. PLoS ONE 2006; 1: E18.
94. Jones AV, Kreil S, Zoi K, Waghorn K, Curtis C, Zhang L et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106: 2162-2168.
95. Steensma DP, Dewald GW, Lasho TL, Powell HL, McClure RF, Levine RL et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106: 1207-1209.
96. Wang SA, Hasserjian RP, Loew JM, Sechman EV, Jones D, Hao S et al. Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features. Leukemia 2006; 20: 1641-1644.
97. Boissinot M, Garand R, Hamidou M, Hermouet S. The JAK2-V617F mutation and essential thrombocythemia features in a subset of patients with refractory anemia with ring sideroblasts (RARS). Blood 2006; 108: 1781-1782.
98. Ceesay MM, Lea NC, Ingram W, Westwood NB, Gaken J, Mohamedali A et al The JAK2 V617F mutation is rare in RARS but common in RARS-T. Leukemia 2006; 20: 2060-2061.
99. Schmitt-Graeff AH, Teo SS, Olschewski M, Schaub F, Haxelmans S, Kirn A et al. JAK2V617F mutation status identifies subtypes of refractory anemia with ringed sideroblasts associated with marked thrombocytosis. Haematologica 2008; 93: 34-40.
100. Johan MF, Goodeve AC, Bowen DT, Frew ME, Reilly JT. JAK2 V617F Mutation is uncommon in chronic myelomonocytic leukaemia. Br J Haematol 2005; 130: 968.
101. Frohling S, Lipka DB, Kayser S, Scholl C, Schlenk RF, Dohner H et al Rare occurrence of the JAK2 V617F mutation in AML subtypes M5, M6, and M7. Blood 2006; 107: 1242-1243.
102. Karow A, Waller C, Reimann C, Niemeyer CM, Kratz CP. JAK2 mutations other than V617F: A novel mutation and mini review. Leuk Res 2008; 32: 365-366.
103. Zhang SJ, Li JY, Li WD, Song JH, Xu W, Qiu HX. The investigation of JAK2 mutation in Chinese myeloproliferative diseases-identification of a novel C616Y point mutation in a PV patient. Int J Lab Hematol 2007; 29: 71-72.
104. Kratz CP, Boll S, Kontny U, Schrappe M, Niemeyer CM, Stanulla M. Mutational screen reveals a novel JAK2 mutation, L611S, in a child with acute lymphoblastic leukemia. Leukemia 2006; 20: 381-383.
105. Malinge S, Ben-Abdelali R, Settegrana C, Radford-Weiss I, Debre M, Beldjord K et al. Novel activating JAK2 mutation in a patient with Down syndrome and B-cell precursor acute lymphoblastic leukemia. Blood 2007; 109: 2202-2204.
106. Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006; 25: 1434-1436.
107. Grunebach F, Bross-Bach U, Kanz L, Brossart P. Detection of a new JAK2 D620E mutation in addition to V617F in a patient with polycythemia vera. Leukemia 2006; 20: 2210-2211.
108. Schnittger S, Bacher U, Kern W, Schroder M, Haferlach T, Schoch C. Report on two novel nucleotide exchanges in the JAK2 pseudokinase domain: D620E and E627E. Leukemia 2006; 20: 2195-2197.
109. Mercher T, Wernig G, Moore SA, Levine RL, Gu TL, Frohling S et al. JAK2T875N is a novel activating mutation that results in myeloproliferative disease with features of megakaryoblastic leukemia in a murine bone marrow transplantation model. Blood 2006; 108: 2770-2779.
110. Butcher CM, Hahn U, To LB, Gecz J, Wilkins EJ, Scott HS et al. Two novel JAK2 exon 12 mutations in JAK2V617F-negative polycythaemia vera patients. Leukemia 2008; 22: 870-873.
111. Williams DM, Kim AH, Rogers O, Spivak JL, Moliterno AR. Phenotypic variations and new mutations in JAK2 V617F-negative polycythemia vera, erythrocytosis, and idiopathic myelofibrosis. Exp Hematol 2007; 35: 1641-1646.
112. Pietra D, Li S, Brisci A, Passamonti F, Rumi E, Theocharides A et al Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 2008; 111 1686-1689.
113. Staerk J, Kallin A, Demoulin JB, Vainchenker W, Constantinescu SN. JAK1 and Tyk2 activation by the homologous polycythemia vera JAK2 V617F mutation: Cross-talk with IGF1 receptor. J Biol Chem 2005; 280 41893-41899.
114. Xiang Z, Zhao Y, Mitaksov V, Fremont DH, Kasai Y, Molitoris A et al Identification of somatic JAK1 mutations in patients with acute myeloid leukemia. Blood 2008; 111: 4809-4812.
115. Inami M, Inokuchi K, Okabe M, Kosaka F, Mitamura Y, Yamaguchi H et al Polycythemia associated with the JAK2V617F mutation emerged during treatment of chronic myelogenous leukemia. Leukemia 2007; 21 1103-1104.
116. Kramer A, Reiter A, Kruth J, Erben P, Hochhaus A, Muller M et al. JAK2-V617F mutation in a patient with Philadelphia-chromosome-positive chronic myeloid leukaemia. Lancet Oncol 2007; 8: 658-660.
117. Hussein K, Bock O, Seegers A, Flasshove M, Henneke F, Buesche G et al Myelofibrosis evolving during imatinib treatment of a chronic myeloproliferative disease with coexisting BCR-ABL translocation and JAK2V617F mutation. Blood 2007; 109: 4106-4107.
118. Scott LM, Campbell PJ, Baxter EJ, Todd T, Stephens P, Edkins S et al The V617F JAK2 mutation is uncommon in cancers and in myeloid malignancies other than the classic myeloproliferative disorders. Blood 2005; 106: 2920-2921.
119. Hussein K, Bock O, Theophile K, Seegers A, Arps H, Basten O et al. Chronic myeloproliferative diseases with concurrent BCR-ABL junction and JAK2(V617F) mutation. Leukemia 2008; 22: 1059-1062.
120. Bornhauser M, Mohr B, Oelschlaegel U, Bornhauser P, Jacki S, Ehninger G et al. Concurrent JAK2(V617F) mutation and BCR-ABL translocation within committed myeloid progenitors in myelofibrosis. Leukemia 2007; 21: 1824-1826.
121. Illmer T, Schaich M, Ehninger G, Thiede C. Tyrosine kinase mutations of JAK2 are rare events in AML but influence prognosis of patients with CBF-leukemias. Haematologica 2007; 92: 137-138.
122. Sotlar K, Bache A, Stellmacher F, Bultmann B, Valent P, Horny HP. Systemic mastocytosis associated with chronic idiopathic myelofibrosis: a distinct subtype of systemic mastocytosis-associated clonal hematological nonmast cell lineage disorder carrying the activating point mutations KITD816V and JAK2V617F. J Mol Diagn 2008; 10 58-66.
123. Sidon P, El HH, Dessars B, Heimann P. The JAK2V617F mutation is detectable at very low level in peripheral blood of healthy donors. Leukemia 2006; 20: 1622.
124. Xu X, Zhang Q, Luo J, Xing S, Li Q, Krantz SB et al. JAK2(V617F): Prevalence in a large Chinese hospital population. Blood 2007; 109: 339-342.
125. Bose S, Deininger M, Gora-Tybor J, Goldman JM, Melo JV. The presence of typical and atypical BCR-ABL fusion genes in leukocytes of normal individuals: Biologic significance and implications for the assessment of minimal residual disease. Blood 1998; 92: 3362-3367.
126. Biernaux C, Loos M, Sels A, Huez G, Stryckmans P. Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals. Blood 1995; 86: 3118-3122.
127. Passamonti F, Rumi E, Pietra D, Lazzarino M, Cazzola M. JAK2 (V617F) mutation in healthy individuals. Br J Haematol 2007; 136: 678-679.
128. McClure R, Mai M, Lasho T. Validation of two clinically useful assays for evaluation of JAK2 V617F mutation in chronic myeloproliferative disorders. Leukemia 2006; 20: 168-171.
129. Bellanne-Chantelot C, Jego P, Lionne-Huyghe P, Tulliez M, Najman A. The JAK2(V617F) mutation may be present several years before the occurrence of overt myeloproliferative disorders. Leukemia 2007; 22: 450-451.
130. Wang YL, Lee JW, Kui JS, Chadburn A, Cross NC, Knowles DM et al. Evaluation of JAK2 in B and T cell neoplasms: Identification of JAK2(V617F) mutation of undetermined significance (JMUS) in the bone marrow of three individuals. Acta Haematol 2007; 118: 209-214.
131. Larsen TS, Christensen JH, Hasselbalch HC, Pallisgaard N. The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders. Br J Haematol 2007; 136: 745-751.
132. Lasho TL, Mesa R, Gilliland DG, Tefferi A. Mutation studies in CD3+, CD19+ and CD34+ cell fractions in myeloproliferative disorders with homozygous JAK2(V617F) in granulocytes. Br J Haematol 2005; 130 797-799.
133. Delhommeau F, Dupont S, Tonetti C, Masse A, Godin I, Le Couedic JP et al. Evidence that the JAK2 G1849T (V617F) mutation occurs in a lympho-myeloid progenitor in polycythemia vera and idiopathic myelofibrosis. Blood 2006; 109: 71-77.
134. Ishii T, Bruno E, Hoffman R, Xu M. Involvement of various hematopoietic-cell lineages by the JAK2V617F mutation in polycythemia vera. Blood 2006; 108: 3128-3134.
135. Adamson JW, Fialkow PJ, Murphy S, Prchal JF, Steinmann L. Polycythemia vera: Stem-cell and probable clonal origin of the disease. N Engl J Med 1976; 295: 913-916.
136. Fujinaka Y, Takane K, Yamashita H, Vasavada RC. Lactogens promote beta cell survival through JAK2/STAT5 activation and BCL-XL upregulation. J Biol Chem 2007; 282: 30707-30717.
137. Walz C, Crowley BJ, Hudon HE, Gramlich JL, Neuberg DS, Podar K et al Activated Jak2 with the V617F point mutation promotes G1/S phase transition. J Biol Chem 2006; 281: 18177-18183.
138. Sattler M, Verma S, Shrikhande G, Byrne CH, Pride YB, Winkler T et al The BCR/ABL tyrosine kinase induces production of reactive oxygen species in hematopoietic cells. J Biol Chem 2000; 275: 24273-24278.
139. Nowicki MO, Falinski R, Koptyra M, Slupianek A, Stoklosa T, Gloc E et al. BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaks. Blood 2004; 104: 3746-3753.
140. Sasaki A, Yasukawa H, Shouda T, Kitamura T, Dikic I, Yoshimura A. CIS3/ SOCS-3 suppresses erythropoietin (EPO) signaling by binding the EPO receptor and JAK2. J Biol Chem 2000; 275: 29338-29347.
141. Hookham MB, Elliott J, Suessmuth Y, Staerk J, Ward AC, Vainchenker W et al. The myeloproliferative disorder-associated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3. Blood 2007; 109: 4924-4929.
142. Theocharides A, Boissinot M, Girodon F, Garand R, Teo SS, Lippert E et al. Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood 2007; 110: 375-379.
143. Campbell PJ, Baxter EJ, Beer PA, Scott LM, Bench AJ, Huntly BJ et al Mutation of JAK2 in the myeloproliferative disorders: Timing, clonality studies, cytogenetic associations, and role in leukemic transformation. Blood 2006; 108: 3548-3555.
144. Lacout C, Pisani DF, Tulliez M, Moreau GF, Vainchenker W, Villeval JL. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 2006; 108: 1652-1660.
145. Scott LM, Scott MA, Campbell PJ, Green AR. Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia. Blood 2006; 108: 2435-2437.
146. Tiedt R, Hao-Shen H, Sobas MA, Looser R, Dirnhofer S, Schwaller J et al. Ratio of mutant JAK2-V617F to wild type JAK2 determines the MPD phenotypes in transgenic mice. Blood 2008; 111: 3931-3940.
147. Shide K, Shimoda HK, Kumano T, Karube K, Kameda T, Takenaka K et al Development of ET, primary myelofibrosis and PV in mice expressing JAK2 V617F. Leukemia 2007; 22: 87-95.
148. Capello D, Deambrogi C, Rossi D, Lischetti T, Piranda D, Cerri M et al. Epigenetic inactivation of suppressors of cytokine signalling in Philadelphia-negative chronic myeloproliferative disorders. Br J Haematol 2008; 141: 504-511.
149. Jost E, do ON, Dahl E, Maintz CE, Jousten P, Habets L et al. Epigenetic alterations complement mutation of JAK2 tyrosine kinase in patients with BCR/ABL-negative myeloproliferative disorders. Leukemia 2007; 21: 505-510.
150. Kralovics R, Teo SS, Li S, Theocharides A, Buser AS, Tichelli A et al Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders. Blood 2006; 108: 1377-1380.
151. Gale RE, Allen AJ, Nash MJ, Linch DC. Long-term serial analysis of X-chromosome inactivation patterns and JAK2 V617F mutant levels in patients with essential thrombocythemia show that minor mutant-positive clones can remain stable for many years. Blood 2007; 109: 1241-1243.
152. Nussenzveig RH, Swierczek SI, Jelinek J, Gaikwad A, Liu E, Verstovsek S et al. Polycythemia vera is not initiated by JAK2(V617F) mutation. Exp Hematol 2007; 35: 32-38.
153. Rumi E, Passamonti F, Pietra D, Delia Porta MG, Arcaini L, Boggi S et al. JAK2 (V617F) as an acquired somatic mutation and a secondary genetic event associated with disease progression in familial myeloproliferative disorders. Cancer 2006; 107: 2206-2211.
154. Lippert E, Boissinot M, Kralovics R, Girodon F, Dobo I, Praloran V et al. The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera. Blood 2006; 108: 1865-1867.
155. Fialkow PJ, Martin PJ, Najfeld V, Penfold GK, Jacobson RJ, Hansen JA. Evidence for a multistep pathogenesis of chronic myelogenous leukemia. Blood 1981; 58: 158-163.
156. Apperley JF, Gardembas M, Melo JV, Russell-Jones R, Bain BJ, Baxter J et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002; 347: 481-487.
157. Baccarani M, Cilloni D, Rondoni M, Ottaviani F, Messa F, Merante S et al. Imatinib mesylate induces complete and durable responses in all patients with the FIP1L1-PDGFRa positive hypereosinophilic syndrome. Results of a multicenter study. Haematologica 2007; 92: 1173-1179.
158. Kantarjian HM, Talpaz M, O'Brien S, Jones D, Giles F, Garcia-Marrero G et al. Survival benefit with imatinib mesylate versus interferon-alpha-based regimens in newly diagnosed chronic-phase chronic myelogenous leukemia. Blood 2006; 108: 1835-1840.
159. Druker BJ, Guilhot F, O'Brien SG, Gathmann I, Kantarjian H, Gattermann N et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006; 355: 2408-2417.
160. Hughes T. ABL kinase inhibitor therapy for CML: Baseline assessments and response monitoring. Hematology Am Soc Hematol Educ Program 2006, 211-218.
161. Hughes T, Branford S. Molecular monitoring of BCR-ABL as a guide to clinical management in chronic myeloid leukaemia. Blood Rev 2006; 20: 29-41.
162. Rousselot P, Huguet F, Rea D, Legros L, Cayuela JM, Maarek O et al Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 2007; 109: 58-60.
163. Graham SM, Jorgensen HG, Allan E, Pearson C, Alcom MJ, Richmond L et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to ST1571 in vitro. Blood 2002; 99: 319-325.
164. Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: Review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006; 108: 28-37.
165. Baccarani M, Saglio G, Goldman J, Hochhaus A, Simonsson B, Appelbaum F et al. Evolving concepts in the management of chronic myeloid leukemia: Recommendations from an expert panel on behalf of the European Leukemia Net. Blood 2006; 108: 1809-1820.
166. Picard S, Titier K, Etienne G, Teilhet E, Ducint D, Bernard MA et al Trough imatinib plasma levels are associated with both cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia. Blood 2007; 109: 3496-3499.
167. Pocaly M, Lagarde V, Etienne G, Ribeil I JA, Claverol S, Bonneu M et al. Overexpression of the heat-shock protein 70 is associated to imatinib resistance in chronic myeloid leukemia. Leukemia 2007; 21: 93-101.
168. White DL, Saunders VA, Dang P, Engler J, Venables A, Zrim S et al. Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: Higher doses of imatinib may overcome the negative impact of low OCT-1 activity. Blood 2007; 110: 4064-4072.
169. Larson RA, Druker BJ, Guilhot FA, O'Brien SG, Riviere GJ, Krahnke T et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: A subanalysis of the IRIS study. Blood 2008; 111: 4022-4028.
170. Wang Y, Cai D, Brendel C, Barett C, Erben P, Manley PW et al. Adaptive secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF) mediates imatinib and nilotinib resistance in BCR/ABL+ progenitors via JAK-2/STAT-5 pathway activation. Blood 2007; 109: 2147-2155.
171. le Coutre P, Ottmann OG, Giles F, Kim DW, Cortes J, Gattermann N et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated phase chronic myelogenous leukemia. Blood 2007; 111: 1834-1839.
172. Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 2007; 110 3540-3546.
173. Kantarjian H, Giles F, Wunderle L, Bhalla K, O'Brien S, Wassmann B et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med 2006; 354: 2542-2551.
174. Rix U, Hantschel O, Durnberger G, Remsing Rix LL, Planyavsky M, Fernbach NV et al. Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets. Blood 2007; 110: 4055-4063.
175. Hantschel O, Rix U, Schmidt U, Burcksturnmer T, Kneidinger M, Schutze G et al. The Btk tyrosine kinase is a major target of the Bcr-Abl inhibitor dasatinib. Proc Natl Acad Sci USA 2007; 104: 13283-13288.
176. von Bubnoff N, Manley PW, Mestan J, Sanger J, Peschel C, Duyster J. Bcr-Abl resistance screening predicts a limited spectrum of point mutations to be associated with clinical resistance to the Abl kinase inhibitor nilotinib (AMN107). Blood 2006; 108: 1328-1333.
177. Soverini S, Martineli G, Colarossi S, Gnani A, Rondoni M, Castagnetti F et al. Second-line treatment with dasatinib in patients resistant to imatinib can select novel inhibitor-specific BCR-ABL mutants in Ph+ ALL. Lancet Oncol 2007; 8: 273-274.
178. Soverini S, Colarossi S, Gnani A, Castagnetti F, Rosti G, Bosi C et al. Resistance to dasatinib in Philadelphia-positive leukemia patients and the presence or the selection of mutations at residues 315 and 317 in the BCR-ABL kinase domain. Haematologica 2007; 92 401-404.
179. Guilhot F, Apperley J, Kim DW, Bullorsky EO, Baccarani M, Roboz GJ et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood 2007; 109: 4143-4150.
180. Shah NP, Kim DW, Kantarjian HM, Rousselot P, Dorlhiac-Llacer PE, Milone JE et al. Dasatinib 50 or 70mg BID compared to 100 or 140mg QD in patients with CML in chronic phase (CP) who are resistant or intolerant to imatinib: One-year results of CA180034. J Clin Oncol 2007; 25 (18S (June 20 Supplement): 7004.
181. Puttini M, Coluccia AM, Boschelli F, Cleris L, Marchesi E, Donella-Deana A et al. In vitro and in vivo activity of SKI-606, a novel Src-Abl inhibitor, against imatinib-resistant Bcr-Abl+ neoplastic cells. Cancer Res 2006; 66: 11314-11322.
182. Konig H, Holyoake TL, Bhatia R. Effective and selective inhibition of chronic myeloid leukemia primitive hematopoietic progenitors by the dual Src/Abl kinase inhibitor SKI-606. Blood 2008; 111: 2329-2338.
183. Morinaga K, Yamauchi T, Kimura S, Maekawa T, Ueda T. Overcoming imatinib resistance using Src inhibitor CGP76030, Abl inhibitor nilotinib and Abl/ Lyn inhibitor INNO-406 in newly established K562 variants with BCR-ABL gene amplification. Int J Cancer 2008; 122: 2621-2627.
184. Deguchi Y, Kimura S, Ashihara E, Niwa T, Hodohara K, Fujiyama Y et al Comparison of imatinib, dasatinib, nilotinib and INNO-406 in imatinib-resistant cell lines. Leuk Res 2008; 32: 980-983.
185. Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ. MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T3151 BCR-ABL mutation. Blood 2007; 109: 500-502.
186. Shah NP, Skaggs BJ, Branford S, Hughes TP, Nicoll JM, Paquette RL et al. Sequential ABL kinase inhibitor therapy selects for compound drug-resistant BCR-ABL mutations with altered oncogenic potency. J Clin Invest 2007; 117: 2562-2569.
187. Thomas DA. Philadelphia chromosome positive acute lymphocytic leukemia: a new era of challenges. Hematology Am Soc Hematol Educ Program 2007; 2007: 435-443.
188. Verstovsek S, Kantarjian H, Pardanani A, Thomas D, Cortes J, Mesa R et al. NCB018424, an oral, selective JAK2 inhibitor, shows significant clinical activity in a Phase I/II Study in patients with primary myelofibrosis (PMF) and post polycythemia vera/essential thrombocythemia myelofibrosis (Post-PV/ET MF). Blood 2007; 110 162.
189. Verstovsek S, Pardanani A, Shah NP, Sokol L, Wadleigh M, Gilliland DG et al. A Phase I Study of XL019, a selective JAK2 inhibitor, in patients with primary myelofibrosis and post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 2007; 110: 162.
190. Pardanani A. JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials. Leukemia 2007; 22: 23-30.
191. Nosaka T, van Deursen JM, Tripp RA, Thierfelder WE, Witthuhn BA, McMickle AP et al. Defective lymphoid development in mice lacking Jak3. Science 1995; 270: 800-802.
192. Guerini V, Barbui V, Spinelli O, Salvi A, Dellacasa C, Carobbio A et al. The histone deacetylase inhibitor ITF2357 selectively targets cells bearing mutated JAK2(V617F). Leukemia 2008; 22: 740-747.
193. Pardanani A, Hood J, Lasho T, Levine RL, Martin MB, Noronha G et al TG101209, a small molecule JAK2-selective kinase inhibitor potently inhibits myeloproliferative disorder-associated JAK2V617F and MPLW515L/K mutations. Leukemia 2007; 21: 1658-1668.
194. Hexner EO, Serdikoff C, Jan M, Swider CR, Robinson C, Yang S et al Lestaurtinib (CEP701)is a JAK2 inhibitor that suppresses JAK2/STAT5 signaling and the proliferation of primary erythroid cells from patients with myeloproliferative disorders. Blood 2008; (in press).
195. Grandage VL, Everington T, Linch DC, Khwaja A. Go6976 is a potent inhibitor of the JAK 2 and FLT3 tyrosine kinases with significant activity in primary acute myeloid leukaemia cells. Br J Haematol 2006; 135: 303-316.
196. Zaleskas VM, Chang WW, Evangelista P, Lazarides K, Chopra R, Zinda M et al. A selective and potent oral inhibitor of the JAK2 tyrosine kinase reverses polycythemia and leukocytosis induced by JAK2 V617F in a mouse model. Blood 2007; 110: 171a.
197. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE et al Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Blood 2007; 110: 171a.
198. Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell 1998; 93: 397-409.