Disordered epigenetic regulation in the pathophysiology of myeloproliferative neoplasms

Current Hematologic Malignancy Reports

Volumn 7, Issue 1, 2012, Pages 34-42

  Zhang, Su Jiang ^a,b   Abdel Wahab, Omar ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^b THE FIRST AFFILIATED HOSPITAL OF NANJING MEDICAL UNIVERSITY   (China)

Author keywords

ASXL1; DNMT3a; Epigenetics; Essentialthrombocytosis; EZH2; H3Y41; IDH1; IDH2; JAK2; L3MBTL1; Mutations; Myelofibrosis; Myeloproliferative neoplasms; Pathophysiology; Polycythemia vera; PRMT5; TET2

Indexed keywords

JANUS KINASE; JANUS KINASE 2; PROTEIN; PROTEIN L3MBTL1; PROTEIN PRMT5; STAT PROTEIN; UNCLASSIFIED DRUG; HISTONE; TUMOR MARKER; TUMOR PROTEIN;

EPIGENETICS; GENE CONTROL; GENE EXPRESSION; GENE MUTATION; GENE TECHNOLOGY; HUMAN; LEUKEMOGENESIS; MYELOPROLIFERATIVE NEOPLASM; NONHUMAN; PATHOPHYSIOLOGY; REVIEW; CELL TRANSFORMATION; DNA METHYLATION; ENZYME ACTIVATION; GENETIC EPIGENESIS; GENETICS; METABOLISM; MUTATION; MYELOPROLIFERATIVE DISORDER; PATHOLOGY; PHOSPHORYLATION;

CELL TRANSFORMATION, NEOPLASTIC; DNA METHYLATION; ENZYME ACTIVATION; EPIGENESIS, GENETIC; HISTONES; HUMANS; JANUS KINASE 2; MUTATION; MYELOPROLIFERATIVE DISORDERS; NEOPLASM PROTEINS; PHOSPHORYLATION; TUMOR MARKERS, BIOLOGICAL;

EID: 84859226893     PISSN: 15588211     EISSN: 1558822X     Source Type: Journal    
DOI: 10.1007/s11899-011-0105-y     Document Type: Review

References (50)

1. James C, et al.A unique clonal JAK2mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434 (7037):1144-8. (Pubitemid 40663494)
2. Kralovics R, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-90. (Pubitemid 40570926)
3. Levine RL, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387-97. (Pubitemid 40544655)
4. Scott LM, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med. 2007;356(5):459-68. (Pubitemid 46193073)
5. Pikman Y, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3 (7):e270.
6. Oh ST, et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood. 2010;116(6):988-92.
7. Beer PA, et al. Clonal diversity in the myeloproliferative neoplasms: independent origins of genetically distinct clones. Br J Haematol. 2009;144(6):904-8.
8. Theocharides A, et al. Leukemic blasts in transformed JAK2-V617F-positive myeloproliferative disorders are frequently negative for the JAK2-V617F mutation. Blood. 2007;110(1):375-9. (Pubitemid 47026857)
9. Levine RL, et al. Role of JAK2 in the pathogenesis and therapy of myeloproliferative disorders. Nat Rev Cancer. 2007;7(9):673-83. (Pubitemid 47327415)
10. Dawson MA, et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009;461 (7265):819-22.
11. Liu F, et al. JAK2V617F-mediated phosphorylation of PRMT5 downregulates its methyltransferase activity and promotes myeloproliferation. Cancer Cell. 2011;19(2):283-94.
12. Griffiths DS, et al. LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease.Nat Cell Biol. 2011;13(1):13-21.
13. Abdel-Wahab O, et al. Concomitant analysis of EZH2 and ASXL1 mutations in myelofibrosis, chronic myelomonocytic leukemia and blast-phase myeloproliferative neoplasms. Leukemia. 2011;25 (7):1200-2.
14. Nikoloski G, et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet. 2010;42(8):665-7.
15. Ernst T, et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet. 2010;42(8):722-6.
16. Guglielmelli P, et al. EZH2 mutational status predicts poor survival in myelofibrosis. Blood. 2011;118(19):5227-34.
17. Su IH, et al. Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol. 2003;4(2):124-31.
18. Lessard J, et al. Functional antagonism of the Polycomb-Group genes eed and Bmi1 in hemopoietic cell proliferation. Genes Dev. 1999;13(20):2691-703. (Pubitemid 29508556)
19. Brecqueville M. Cervera, N, Adélaide, J, Rey, J, Carbuccia, N, Chaffanet, M, Mozziconacci, M J, Vey, N, Birnbaum, D, Gelsi-Boyer, V, and A Murati, Mutations and deletions of the SUZ12 polycomb gene in myeloproliferative neoplasms. Blood Cancer Journal. 2011;1:e33.
20. Bench, A.J., et al., Chromosome 20 deletions in myeloidmalignancies: reduction of the common deleted region, generation of a PAC/BAC contig and identification of candidate genes. UK Cancer CytogeneticsGroup (UKCCG). Oncogene, 2000. 19(34):3902-13. (Pubitemid 30658981)
21. Min J, et al. L3MBTL1 recognition of mono-and dimethylated histones. Nat Struct Mol Biol. 2007;14(12):1229-30. (Pubitemid 350223338)
22. Perna F, et al. Depletion of L3MBTL1 promotes the erythroid differentiation of human hematopoietic progenitor cells: possible role in 20q-polycythemia vera. Blood. 2010;116(15):2812-21.
23. Gelsi-Boyer V, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocyticleukaemia. Br J Haematol. 2009;145(6):788-800.
24. Abdel-Wahab O, et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. CancerRes. 2010;70(2):447-52.
25. Carbuccia N, et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia. 2009;23(11):2183-6.
26. Abdel-Wahab, O., et al., The most commonly reported variant in ASXL1 (c.1934dupG;p.Gly646TrpfsX12) is not a somatic alteration. Leukemia, 2010. 24(9):1656-7.
27. Scheuermann JC, et al. Histone H2A deubiquitinase activity of the Polycomb repressive complex PR-DUB. Nature. 2010;465 (7295):243-7.
28. Fisher, C.L., et al., Loss-of-function Additional sex combs-like1 mutations disrupt hematopoiesis but do not cause severe myelodysplasiaor leukemia. Blood, 2009.
29. Hoischen A, et al. De novo nonsense mutations in ASXL1 cause Bohring-Opitz syndrome. Nat Genet. 2011;43(8):729-31.
30. Delhommeau F, et al. Mutation in TET2 in myeloid cancers. N Engl J Med. 2009;360(22):2289-301.
31. Langemeijer SM, et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet. 2009;41(7):838-42.
32. Cimmino L, et al. TET Family Proteins and Their Role in Stem Cell Differentiation and Transformation. Cell Stem Cell. 2011;9(3):193-204.
33. Ko M, et al. Impaired hydroxylation of 5-methylcytosine in myeloid cancers with mutant TET2. Nature. 2010;468(7325):839-43.
34. Tefferi A, et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis.Leukemia. 2009;23(5):905-11.
35. Li, Z., et al., Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid malignancies. Blood, 2011.
36. Moran-Crusio, K., et al., Tet2 loss leads to increased hematopoietic stem cell self-renewal and myeloid transformation. Cancer Cell, 2011. 20(1):11-24. revealed that deletion of Tet2 in vivo drives myeloid transformation and is linked with loss of 5-hydroxymethylcytosine. This study and the study by Quivoron et al. [37] revealed thatdeletion of Tet2 in vivo drives myeloid transformation and is linked with loss of 5-hydroxymethylcytosine.
37. Quivoron, C., et al., TET2 inactivation results in pleiotropichematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell, 2011. 20(1):25-38 This study and the study by Moran-Crusio et al. [36] revealed that deletion of Tet2 in vivo drives myeloid transformation and is linked with loss of 5-hydroxymethylcytosine.
38. Ko M, et al. Ten-Eleven-Translocation 2 (TET2) negatively regulates homeostasis and differentiation of hematopoietic stem cells in mice. Proc Natl Acad Sci U S A. 2011;108(35):14566-71.
39. Ley TJ, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424-33.
40. Yan XJ, et al. Exome sequencing identifies somatic mutations of DNA methyltransferase gene DNMT3A in acute monocytic leukemia. Nat Genet. 2011;43(4):309-15.
41. Yamashita Y, et al. Array-based genomic resequencing of human leukemia. Oncogene. 2010;29(25):3723-31.
42. Abdel-Wahab, O., et al., DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia, 2011
43. Stegelmann F, et al. DNMT3A mutations in myeloproliferative neoplasms. Leukemia. 2011;25(7):1217-9.
44. Walter, M., Shen, D, Shao, J, Ding, L, Grillot, M, McLellan, M, Fulton, R, Schmidt, H, Kalicki-Veizer, J, O'Laughlin, M, Westervelt, P, DiPersio, JF, Mardis, ER, Wilson, R, Ley, TJ and Timothy Graubert, Recurrent DNMT3A Mutations In Patients with Myelodysplastic Syndrome. Leukemia (in press),2011.
45. Tadokoro Y, et al. De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med. 2007;204(4):715-22. (Pubitemid 46631602)
46. Tefferi A, et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic-or blast-phase essential thrombocythemia,polycythemia vera or myelofibrosis. Leukemia. 2010;24(7):1302-9.
47. Tefferi, A., et al., IDH mutations in primary myelofibrosis predict leukemic transformation and shortened survival: clinical evidence for leukemogenic collaboration with JAK2V617F. Leukemia, 2011.
48. Dang L, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature. 2009;462(7274):739-44.
49. Xu, W., et al., Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of alpha-ketoglutarate-dependent dioxygenases. Cancer Cell, 2011. 19(1):17-30. This study and the study by Figueroa et al. [50] identified that ?-ketoglutarate-dependent enzymes, including the TET and Jumonji histone lysine demethylase family, are inhibited by the presence of 2-HG produced by mutant IDH1/2.
50. Figueroa, M.E., et al., Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell, 2010. 18 (6):553-67. This study and the study by Xu et al. [49] identified that ?-ketoglutarate-dependent enzymes, including the TET andJumonji histone lysine demethylase family, are inhibited by the presence of 2-HG produced by mutant IDH1/2.