Role of Germline Genetic Factors in MPN Pathogenesis

Hematology/Oncology Clinics of North America

Volumn 26, Issue 5, 2012, Pages 1037-1051

  Harutyunyan, Ashot S ^a   Kralovics, Robert ^a,b  

^a ERICH SCHMID INSTITUTE OF MATERIALS SCIENCE   (Austria)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Familial clustering; Germline variants; Hereditary predisposition; JAK2 haplotype; Myeloproliferative neoplasms; Penetrance

Indexed keywords

HEMOGLOBIN; JANUS KINASE 2; STAT1 PROTEIN; THROMBOPOIETIN; XERODERMA PIGMENTOSUM GROUP D PROTEIN;

ACUTE GRANULOCYTIC LEUKEMIA; ALLELE; CHROMOSOME ABERRATION; DISEASE COURSE; EPOR GENE; ERYTHROCYTOSIS; FAMILIAL DISEASE; GENETIC POLYMORPHISM; GENETIC PREDISPOSITION; GENETIC SUSCEPTIBILITY; GENETIC TRANSFORMATION; GENETIC VARIABILITY; HAPLOTYPE; HEMATOPOIESIS; HEREDITY; HETEROZYGOSITY; HUMAN; JUVENILE MYELOMONOCYTIC LEUKEMIA; MPL GENE; MYELODYSPLASTIC SYNDROME; MYELOPROLIFERATIVE NEOPLASM; ONCOGENE; OXYGEN AFFINITY; OXYGEN SENSING; PATHOGENESIS; POINT MUTATION; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; RISK; THROMBOCYTOSIS;

CELL TRANSFORMATION, NEOPLASTIC; CHROMOSOME ABERRATIONS; GERM CELLS; HUMANS; MYELOPROLIFERATIVE DISORDERS; PROGNOSIS;

EID: 84866620565     PISSN: 08898588     EISSN: 15581977     Source Type: Journal    
DOI: 10.1016/j.hoc.2012.07.005     Document Type: Review

References (76)

1. Tefferi A., Vardiman J.W. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008, 22:14.
2. Campbell P.J., Green A.R. The myeloproliferative disorders. N Engl J Med 2006, 355:2452.
3. Dingli D., Schwager S.M., Mesa R.A., et al. Presence of unfavorable cytogenetic abnormalities is the strongest predictor of poor survival in secondary myelofibrosis. Cancer 2006, 106:1985.
4. Bellanne-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.
5. Ostgard L.S., Kjeldsen E., Holm M.S., et al. Reasons for treating secondary AML as de novo AML. Eur J Haematol 2010, 85:217.
6. Tefferi A., Vainchenker W. Myeloproliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol 2011, 29:573.
7. Baxter E.J., Scott L.M., Campbell P.J., et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005, 365:1054.
8. James C., Ugo V., Le Couedic J.P., et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005, 434:1144.
9. Kralovics R., Passamonti F., Buser A.S., et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005, 352:1779.
10. Levine R.L., 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.
11. Pietra D., Li S., Brisci A., et al. Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 2008, 111:1686.
12. Scott L.M., Tong W., Levine R.L., et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007, 356:459.
13. Pikman Y., Lee B.H., Mercher T., et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006, 3:e270.
14. Delhommeau F., Dupont S., Della Valle V., et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009, 360:2289.
15. Langemeijer S.M., Kuiper R.P., Berends M., et al. Acquired mutations in TET2 are common in myelodysplastic syndromes. Nat Genet 2009, 41:838.
16. Tefferi A., Pardanani A., Lim K.H., et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 2009, 23:905.
17. Dunbar A.J., Gondek L.P., O'Keefe C.L., et al. 250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies. Cancer Res 2008, 68:10349.
18. Sanada M., Suzuki T., Shih L.Y., et al. Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. Nature 2009, 460:904.
19. Ernst T., Chase A.J., Score J., et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010, 42:722.
20. Nikoloski G., Langemeijer S.M., Kuiper R.P., et al. Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes. Nat Genet 2010, 42:665.
21. Carbuccia N., Murati A., Trouplin V., et al. Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 2009, 23:2183.
22. Beer P.A., Delhommeau F., LeCouedic J.P., et al. Two routes to leukemic transformation after a JAK2 mutation-positive myeloproliferative neoplasm. Blood 2010, 115:2891.
23. Harutyunyan A., Klampfl T., Cazzola M., et al. p53 lesions in leukemic transformation. N Engl J Med 2011, 364:488.
24. Ding Y., Harada Y., Imagawa J., et al. AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 2009, 114:5201.
25. Klampfl T., Harutyunyan A., Berg T., et al. Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 2011, 118:167.
26. Falini B., Mecucci C., Tiacci E., et al. Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. N Engl J Med 2005, 352:254.
27. Green A., Beer P. Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 2010, 362:369.
28. Pardanani A., Lasho T.L., Finke C.M., et al. IDH1 and IDH2 mutation analysis in chronic- and blast-phase myeloproliferative neoplasms. Leukemia 2010, 24:1146.
29. Tefferi A., Lasho T.L., Abdel-Wahab O., et al. IDH1 and IDH2 mutation studies in 1473 patients with chronic-, fibrotic- or blast-phase essential thrombocythemia, polycythemia vera or myelofibrosis. Leukemia 2010, 24:1302.
30. Thoennissen N.H., Krug U.O., Lee D.H., et al. Prevalence and prognostic impact of allelic imbalances associated with leukemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms. Blood 2010, 115:2882.
31. Rumi E., Harutyunyan A., Elena C., et al. Identification of genomic aberrations associated with disease transformation by means of high-resolution SNP array analysis in patients with myeloproliferative neoplasm. Am J Hematol 2011, 86:974.
32. Pardanani A., Fridley B.L., Lasho T.L., et al. Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood 2008, 111:2785.
33. Wernig G., Gonneville J.R., Crowley B.J., et al. The Jak2V617F oncogene associated with myeloproliferative diseases requires a functional FERM domain for transformation and for expression of the Myc and Pim proto-oncogenes. Blood 2008, 111:3751.
34. Beer P.A., Jones A.V., Bench A.J., et al. Clonal diversity in the myeloproliferative neoplasms: independent origins of genetically distinct clones. Br J Haematol 2009, 144:904.
35. Beer P.A., Ortmann C.A., Campbell P.J., et al. Independently acquired biallelic JAK2 mutations are present in a minority of patients with essential thrombocythemia. Blood 2010, 116:1013.
36. Hussein K., Bock O., Theophile K., et al. Biclonal expansion and heterogeneous lineage involvement in a case of chronic myeloproliferative disease with concurrent MPLW515L/JAK2V617F mutation. Blood 2009, 113:1391.
37. Kralovics R. Genetic complexity of myeloproliferative neoplasms. Leukemia 2008, 22:1841.
38. Olcaydu D., Harutyunyan A., Jager R., et al. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet 2009, 41:450.
39. Landgren O., Goldin L.R., Kristinsson S.Y., et al. Increased risks of polycythemia vera, essential thrombocythemia, and myelofibrosis among 24,577 first-degree relatives of 11,039 patients with myeloproliferative neoplasms in Sweden. Blood 2008, 112:2199.
40. Rumi E., Passamonti F., Della Porta M.G., et al. Familial chronic myeloproliferative disorders: clinical phenotype and evidence of disease anticipation. J Clin Oncol 2007, 25:5630.
41. Jones A.V., Chase A., Silver R.T., et al. JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet 2009, 41:446.
42. Kilpivaara O., Mukherjee S., Schram A.M., et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet 2009, 41:455.
43. Olcaydu D., Skoda R.C., Looser R., et al. The 'GGCC' haplotype of JAK2 confers susceptibility to JAK2 exon 12 mutation-positive polycythemia vera. Leukemia 2009, 23:1924.
44. Jones A.V., Campbell P.J., Beer P.A., et al. The JAK2 46/1 haplotype predisposes to MPL-mutated myeloproliferative neoplasms. Blood 2010, 115:4517.
45. Pardanani A., Lasho T.L., Finke C.M., 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.
46. Tefferi A., Lasho T.L., Patnaik M.M., et al. JAK2 germline genetic variation affects disease susceptibility in primary myelofibrosis regardless of V617F mutational status: nullizygosity for the JAK2 46/1 haplotype is associated with inferior survival. Leukemia 2010, 24:105.
47. Kralovics R., Stockton D.W., Prchal J.T. Clonal hematopoiesis in familial polycythemia vera suggests the involvement of multiple mutational events in the early pathogenesis of the disease. Blood 2003, 102:3793.
48. Rumi E. Familial chronic myeloproliferative disorders: the state of the art. Hematol Oncol 2008, 26:131.
49. Olcaydu D., Rumi E., Harutyunyan A., et al. The role of the JAK2 GGCC haplotype and the TET2 gene in familial myeloproliferative neoplasms. Haematologica 2011, 96:367.
50. Rumi E., Passamonti F., Picone C., et al. Disease anticipation in familial myeloproliferative neoplasms. Blood 2008, 112:2587.
51. Rumi E., Passamonti F., Pietra D., 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.
52. Skoda R. The genetic basis of myeloproliferative disorders. Hematology Am Soc Hematol Educ Program 2007, 1-10.
53. Kralovics R., Skoda R.C. Molecular pathogenesis of Philadelphia chromosome negative myeloproliferative disorders. Blood Rev 2005, 19:1.
54. Ang S.O., Chen H., Hirota K., et al. Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia. Nat Genet 2002, 32:614.
55. Albiero E., Ruggeri M., Fortuna S., et al. Analysis of the oxygen sensing pathway genes in familial chronic myeloproliferative neoplasms and identification of a novel EGLN1 germ-line mutation. Br J Haematol 2011, 153:405.
56. de la Chapelle A., Traskelin A.L., Juvonen E. Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis. Proc Natl Acad Sci U S A 1993, 90:4495.
57. Liu K., Kralovics R., Rudzki Z., et al. A de novo splice donor mutation in the thrombopoietin gene causes hereditary thrombocythemia in a Polish family. Haematologica 2008, 93:706.
58. Wiestner A., Schlemper R.J., van der Maas A.P., et al. An activating splice donor mutation in the thrombopoietin gene causes hereditary thrombocythaemia. Nat Genet 1998, 18:49.
59. 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.
60. El-Harith el H.A., Roesl C., Ballmaier M., et al. Familial thrombocytosis caused by the novel germ-line mutation p.Pro106Leu in the MPL gene. Br J Haematol 2009, 144:185.
61. Lambert M.P., Jiang J., Batra V., et al. A novel mutation in MPL (Y252H) results in increased thrombopoietin sensitivity in essential thrombocythemia. Am J Hematol 2012, 87:532.
62. Moliterno A.R., Williams D.M., Gutierrez-Alamillo L.I., et al. Mpl Baltimore: a thrombopoietin receptor polymorphism associated with thrombocytosis. Proc Natl Acad Sci U S A 2004, 101:11444.
63. Teofili L., Giona F., Martini M., et al. Markers of myeloproliferative diseases in childhood polycythemia vera and essential thrombocythemia. J Clin Oncol 2007, 25:1048.
64. Teofili L., Giona F., Torti L., et al. Hereditary thrombocytosis caused by MPLSer505Asn is associated with a high thrombotic risk, splenomegaly and progression to bone marrow fibrosis. Haematologica 2010, 95:65.
65. Etheridge L., Corbo L.M., Kaushansky K., et al. A Novel activating JAK2 mutation, JAK2R564Q, causes familial essential thrombocytosis (fET) via mechanisms distinct from JAK2V617F. Blood (ASH Annual Meeting Abstracts) 2011, 118(21):123.
66. Mead A.J., Rugless M.J., Jacobsen S.E., et al. Germline JAK2 mutation in a family with hereditary thrombocytosis. N Engl J Med 2012, 366:967.
67. Rumi E., Harutyunyan A., Pietra D., et al. A novel germline JAK2 mutation in familial thrombocytosis. Haematologica 2012, 97(s1):244.
68. Smith M.L., Cavenagh J.D., Lister T.A., et al. Mutation of CEBPA in familial acute myeloid leukemia. N Engl J Med 2004, 351:2403.
69. Hahn C.N., Chong C.E., Carmichael C.L., et al. Heritable GATA2 mutations associated with familial myelodysplastic syndrome and acute myeloid leukemia. Nat Genet 2011, 43:1012.
70. Song W.J., Sullivan M.G., Legare R.D., et al. Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nat Genet 1999, 23:166.
71. Yamaguchi H., Baerlocher G.M., Lansdorp P.M., et al. Mutations of the human telomerase RNA gene (TERC) in aplastic anemia and myelodysplastic syndrome. Blood 2003, 102:916.
72. Kirwan M., Vulliamy T., Marrone A., et al. Defining the pathogenic role of telomerase mutations in myelodysplastic syndrome and acute myeloid leukemia. Hum Mutat 2009, 30:1567.
73. Niemeyer C.M., Kang M.W., Shin D.H., et al. Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia. Nat Genet 2010, 42:794.
74. Chen E., Beer P.A., Godfrey A.L., et al. Distinct clinical phenotypes associated with JAK2V617F reflect differential STAT1 signaling. Cancer Cell 2010, 18:524.
75. Hernandez-Boluda J.C., Pereira A., Cervantes F., et al. A polymorphism in the XPD gene predisposes to leukemic transformation and new nonmyeloid malignancies in essential thrombocythemia and polycythemia vera. Blood 2012, 119:5221.
76. Harutyunyan A., Gisslinger B., Klampfl T., et al. Rare germline variants in regions of loss of heterozygosity may influence clinical course of hematological malignancies. Leukemia 2011, 25:1782.