Polycythemia vera and essential thrombocythemia: New developments in biology with therapeutic implications

Current Opinion in Hematology

Volumn 20, Issue 2, 2013, Pages 169-175

  Soriano, Gabriela ^a   Heaney, Mark ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

epigenetic changes; JAK2V617F; janus kinase signal transducer and activator of transcription signalling

Indexed keywords

DNA METHYLTRANSFERASE 3A; IKAROS TRANSCRIPTION FACTOR; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; JANUS KINASE; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; NEUROFIBROMIN; PROTEIN P53; STAT PROTEIN; TRANSCRIPTION FACTOR EZH2; TRANSCRIPTION FACTOR RUNX1;

CELL GROWTH; CELL PROLIFERATION; CELL SURVIVAL; DISEASE COURSE; EPIGENETICS; EXON; GENE DOSAGE; HOMOZYGOSITY; HUMAN; INTRACELLULAR SIGNALING; NONHUMAN; PHENOTYPE; POLYCYTHEMIA VERA; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; THROMBOCYTHEMIA;

DISEASE PROGRESSION; HUMANS; JANUS KINASE 2; MUTATION; PHENOTYPE; POLYCYTHEMIA VERA; THROMBOCYTHEMIA, ESSENTIAL;

EID: 84873411400     PISSN: 10656251     EISSN: 15317048     Source Type: Journal    
DOI: 10.1097/MOH.0b013e32835d82fe     Document Type: Review

References (61)

1. Levine RL, Wadleigh M, Cools J, 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.
2. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352:1779-1790.
3. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434:1144-1148.
4. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365:1054-1061.
5. Cross NC. Current Issues in myeloproliferative neoplasms: Genetic and epigenetic complexity in myeloproliferative neoplasms. Hematology Am Soc Hematol Educ Program Book 2011; 2011:208-214.
6. Vainchenker W, Constantinescu SN. JAK/STAT signaling in hematological malignancies. Oncogene 2012. [Epub ahead of print].
7. Vainchenker W, Delhommeau Fo, Constantinescu SN, et al. New mutations and pathogenesis of myeloproliferative neoplasms. Blood 2011; 118:1723-1735.
8. Hookham MB, Elliott J, Suessmuth Y, et al. The myeloproliferative disorderassociated JAK2 V617F mutant escapes negative regulation by suppressor of cytokine signaling 3. Blood 2007; 109:4924-4929.
9. Liu F, Zhao X, Perna F, et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell 2011; 19:283-294.
10. Dawson MA, Bannister AJ, Gottgens B, et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature 2009; 461:819-822.
11. Scott LM, Rebel VI. JAK2 and genomic instability in the myeloproliferative neoplasms: a case of the chicken or the egg? Am J Hematol 2012; 87:1028-1036.
12. Tefferi A, Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011; 29:573-582.
13. Vannucchi AM, Guglielmelli P, Tefferi A. Advances in understanding and management of myeloproliferative neoplasms. Cancer 2009; 59:171-191.
14. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008; 22:1299-1307.
15. Passamonti F, Rumi E, Pietra D, et al. A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 2010; 24:1574-1579.
16. Barbui T, Thiele J, Passamonti F, et al. Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 2011; 29:3179-3184.
17. Godfrey AL, Chen E, Pagano F, et al. JAK2V617F homozygosity arises commonly and recurrently in PV and ET, but PV is characterized by expansion of a dominant homozygous subclone. Blood 2012; 120:2704-2707.
18. Campbell PJ, Scott LM, Buck G, et al. Definition of subtypes of essential thrombocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366:1945-1953.
19. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Clinical profile of homozygous JAK2 617VF mutation in patients with polycythemia vera or essential thrombocythemia. Blood 2007; 110:840-846.
20. Lacout C, Pisani DF, Tulliez M, et al. JAK2V617F expression in murine hematopoietic cells leads to MPD mimicking human PV with secondary myelofibrosis. Blood 2006; 108:1652-1660.
21. Marty C, Lacout C, Martin A, et al. Myeloproliferative neoplasm induced by constitutive expression of JAK2V617F in knock-in mice. Blood 2010; 116:783-787.
22. Wernig G, Mercher T, Okabe R, et al. Expression of Jak2V617F causes a polycythemia vera-like disease with associated myelofibrosis in a murine bone marrow transplant model. Blood 2006; 107:4274-4281.
23. Mullally A, Lane SW, Ball B, et al. Physiological Jak2V617F expression causes a lethal myeloproliferative neoplasm with differential effects on hematopoietic stem and progenitor cells. Cancer Cell 2010; 17:584-596.
24. Tiedt R, Hao-Shen H, Sobas MA, et al. Ratio of mutant JAK2-V617F to wildtype Jak2 determines the MPD phenotypes in transgenic mice. Blood 2008; 111:3931-3940.
25. Akada H, Yan D, Zou H, et al. Conditional expression of heterozygous or homozygous Jak2V617F from its endogenous promoter induces a polycythemia vera-like disease. Blood 2010; 115:3589-3597.
26. Jones AV, Kreil S, Zoi K, et al. Widespread occurrence of the JAK2 V617F mutation in chronic myeloproliferative disorders. Blood 2005; 106:2162-2168.
27. Levine RL, Belisle C, Wadleigh M, et al. X-inactivation-based clonality analysis and quantitative JAK2V617F assessment reveal a strong association between clonality and JAK2V617F in PV but not ET/MMM, and identifies a subset of JAK2V617F-negative ET and MMM patients with clonal hematopoiesis. Blood 2006; 107:4139-4141.
28. Bellanné-Chantelot C, Chaumarel I, Labopin M, et al. Genetic and clinical implications of the Val617Phe JAK2 mutation in 72 families with myeloproliferative disorders. Blood 2006; 108:346-352.
29. Schaub FX, Jager R, Looser R, et al. Clonal analysis of deletions on chromosome 20q and JAK2-V617F in MPD suggests that del20q acts independently and is not one of the predisposing mutations for JAK2-V617F. Blood 2009; 113:2022-2027.
30. Schaub FX, Looser R, Li S, et al. Clonal analysis of TET2 and JAK2 mutations suggests that TET2 can be a late event in the progression of myeloproliferative neoplasms. Blood 2003; 115:7.
31. Swierczek SI, Yoon D, Bellanne-Chantelot C, et al. Extent of hematopoietic involvement by TET2 mutations in JAK2V(6)(1)(7)F polycythemia vera. Haematologica 2011; 96:775-778.
32. Dupont S, Masse A, James C, et al. The JAK2 617VF mutation triggers erythropoietin hypersensitivity and terminal erythroid amplification in primary cells from patients with polycythemia vera. Blood 2007; 110:1013-1021.
33. Moliterno AR, Williams DM, Rogers O, et al. Phenotypic variability within the JAK2 V617F-positive MPD: roles of progenitor cell and neutrophil allele burdens. Experiment Hematol 2008; 36:1480-1486.
34. Levine RL, Wernig G. Role of JAK-STAT signaling in the pathogenesis of myeloproliferative disorders. Hematology Am Soc Hematol Educ Program 2006; 510:233-239.
35. Tefferi A. Primary myelofibrosis: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 2011; 86:1017-1026.
36. Schnittger S, Bacher U, Eder C, et al. Molecular analyses of 15,542 patients with suspected BCR-ABL1-negative myeloproliferative disorders allow to develop a stepwise diagnostic workflow. Haematologica 2012; 97:1582-1585.
37. Passamonti F, Elena C, Schnittger S, et al. Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations. Blood 2011; 117:2813-2816.
38. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112:141-149.
39. Ding J, Komatsu H, Wakita A, et al. Familial essential thrombocythemia associated with a dominant-positive activating mutation of the c-MPL gene, which encodes for the receptor for thrombopoietin. Blood 2004; 103:4198-4200.
40. Liu K, Martini M, Rocca B, et al. Evidence for a founder effect of the MPLS505N mutation in eight Italian pedigrees with hereditary thrombocythemia. Haematologica 2009; 94:1368-1374.
41. Bersenev A, Wu C, Balcerek J, et al. Lnk constrains myeloproliferative diseases in mice. J Clin Invest 2010; 120:2058-2069.
42. Pardanani A, Lasho TL, Finke CM, et al. The JAK2 46/1 haplotype confers susceptibility to essential thrombocythemia regardless of JAK2V617F mutational status: clinical correlates in a study of 226 consecutive patients. Leukemia 2010; 24:110-114.
43. Abdel-Wahab O, Pardanani A, Patel J, et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia 2011; 25:1200-1202.
44. Abdel-Wahab O, Tefferi A, Levine RL. Role of TET2 and ASXL1 mutations in the pathogenesis of myeloproliferative neoplasms. Hematol Oncol Clin N Am 2012; 26:1053-1064.
45. Abdel-Wahab O, Pardanani A, Rampal R, et al. DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia 2011; 25:1219-1220.
46. Quivoron C, Couronne L, Della Valle V, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer cell 2011; 20:25-38.
47. Moran-Crusio K, Reavie L, Shih A, et al. Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell 2011; 20:11-24.
48. Martinez-Aviles L, Besses C, Alvarez-Larran A, et al. TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2-and MPL-negative myeloproliferative
49. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009; 360:2289-2301.
50. Vannucchi AM, Biamonte F. Epigenetics and mutations in chronic myeloproliferative neoplasms. Haematologica 2011; 96:1398-1402.
51. Tefferi A. Polycythemia vera and essential thrombocythemia: 2012 update on diagnosis, risk stratification, and management. Am J Hematol 2012; 87:285-293.
52. Guglielmelli P, Biamonte F, Score J, et al. EZH2 mutational status predicts poor survival in myelofibrosis. Blood 2011; 118:5227-5234.
53. Shih AH, Abdel-Wahab O, Patel JP, et al. The role of mutations in epigenetic regulators in myeloid malignancies. Nature Rev Cancer 2012; 12:599-612.
54. Tefferi A. Novel mutations and their functional and clinical relevance in myeloproliferative neoplasms: JAK2, MPL, TET2, ASXL1, CBL, IDH and IKZF1. Leukemia 2010; 24:1128-1138.
55. Green A, Beer P. Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 2010; 362:369-370.
56. Zhang SJ, Rampal R, Manshouri T, et al. Genetic analysis of patients with leukemic transformation of myeloproliferative neoplasms shows recurrent SRSF2 mutations that are associated with adverse outcome. Blood 2012; 119:4480-4485.
57. Harutyunyan A, Klampfl T, Cazzola M, et al. p53 lesions in leukemic transformation. N Engl J Med 2011; 364:488-490.
58. Ichikawa M, Asai T, Chiba S, et al. Runx1/AML-1 ranks as a master regulator of adult hematopoiesis. Cell Cycle 2004; 3:722-724.
59. Yamagata T, Maki K, Mitani K. Runx1/AML1 in normal and abnormal hematopoiesis. Int J Hematol 2005; 82:1-8.
60. Ding Y, Harada Y, Imagawa J, et al. AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 2009; 114:5201-5205.
61. Verstovsek S, Kantarjian HM, Estrov Z, et al. Long term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood 2012; 120:2768-2769.