BCR-ABL1-negative myeloproliferative neoplasms: A review of molecular biology, diagnosis, and treatment

Clinical Lymphoma, Myeloma and Leukemia

Volumn 11, Issue SUPPL.1, 2011, Pages

  Vakil, Erik ^a   Tefferi, Ayalew ^b  

^a ROYAL COLLEGE OF SURGEONS IN IRELAND   (Ireland)

^b MAYO CLINIC   (United States)

Author keywords

Cytogenetics; Diagnostic strategy; Oncogenes

Indexed keywords

ACETYLSALICYLIC ACID; ANDROGEN; BCR ABL PROTEIN; BUSULFAN; DANAZOL; FLUOXYMESTERONE; HYDROXYUREA; JANUS KINASE 2; JANUS KINASE INHIBITOR; LENALIDOMIDE; MOLECULAR MARKER; PEGINTERFERON ALPHA; PREDNISONE; RECOMBINANT ALPHA INTERFERON; RUXOLITINIB; STEROID; TESTOSTERONE ENANTATE; TG101384; THALIDOMIDE; UNCLASSIFIED DRUG;

ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION; ANEMIA; BLEEDING; CANCER CHEMOTHERAPY; CANCER RADIOTHERAPY; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL (TOPIC); CONFERENCE PAPER; CYTOGENETICS; DATA ANALYSIS; DISEASE CLASSIFICATION; DRUG EFFICACY; DRUG MEGADOSE; GASTROINTESTINAL HEMORRHAGE; HEPATOMEGALY; HUMAN; LEUKOCYTOSIS; LOW DRUG DOSE; MEDICAL RECORD; MOLECULAR BIOLOGY; MORTALITY; MUTATION; MYELOID METAPLASIA; MYELOPROLIFERATIVE NEOPLASM; ONCOGENE; PATHOGENICITY; PHASE 2 CLINICAL TRIAL (TOPIC); PHLEBOTOMY; POLYCYTHEMIA VERA; PROGNOSIS; SPLENECTOMY; SPLENOMEGALY; THROMBOCYTHEMIA; THROMBOCYTOPENIA; THROMBOSIS; THROMBOTIC THROMBOCYTOPENIC PURPURA; UNSPECIFIED SIDE EFFECT; WORLD HEALTH ORGANIZATION;

EID: 84859022243     PISSN: 21522650     EISSN: 21522669     Source Type: Journal    
DOI: 10.1016/j.clml.2011.04.002     Document Type: Conference Paper

References (128)

1. Dameshek W. Some speculations on the myeloproliferative syndromes. Blood 1951; 6:372-5.
2. Vardiman JW, Brunning RD, Harris NL. WHO histological classification of chronic myeloproliferative diseases. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds. World Health Organization Classification of Tumors: Tumors of the Haematopoietic and Lymphoid Tissues. Lyon, France: International Agency for Research on Cancer (IARC) Press; 2001: 17-44.
3. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009; 114:937-51.
4. Nowell PC, Hungerford DA. A minute chromosome in human granulocytic leukemia. Science 1960; 132:1497.
5. Kelliher MA, McLaughlin J, Witte ON, Rosenberg N. Induction of a chronic myelogenous leukemia-like syndrome in mice with v-abl and BCR/ABL. Proc Natl Acad Sci USA 1990; 87:6649-53.
6. Daley GQ, Baltimore D. Transformation of an interleukin 3-dependent hematopoietic cell line by the chronic myelogenous leukemia-specific P210bcr/abl protein. Proc Natl Acad Sci USA 1988; 85:9312-6.
7. Elefanty AG, Hariharan IK, Cory S. bcr-abl, the hallmark of chronic myeloid leukaemia in man, induces multiple haemopoietic neoplasms in mice. Embo J 1990; 9:1069-78.
8. 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; 7:387-97.
9. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434:1144-8.
10. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 2005; 352:1779-90.
11. Rollison DE, Howlader N, Smith MT, et al. Epidemiology of myelodysplastic syndromes and chronic myeloproliferative disorders in the United States, 2001-2004, using data from the NAACCR and SEER programs. Blood 2008; 112:45-52.
12. Gangat N, Strand J, Lasho TL, et al. Cytogenetic studies at diagnosis in polycythemia vera: clinical and JAK2V617F allele burden correlates. Eur J Haematol 2008; 80:197-200.
13. Gangat N, Tefferi A, Thanarajasingam G, et al. Cytogenetic abnormalities in essential thrombocythemia: prevalence and prognostic significance. Eur J Haematol 2009; 83:17-21.
14. Hussein K, Huang J, Lasho T, et al. Karyotype complements the International Prognostic Scoring System for primary myelofibrosis. Eur J Haematol 2009; 82: 255-9.
15. Hussein K, Pardanani AD, Van Dyke DL, Hanson CA, Tefferi A. International Prognostic Scoring System: independent cytogenetic risk categorization in primary myelofibrosis. Blood 2010; 115:496-9.
16. Verstovsek S, Silver RT, Cross NC, Tefferi A. JAK2V617F mutational frequency in polycythemia vera: 100%, <90%, less? Leukemia 2006; 20:2067.
17. Tefferi A, Lasho TL, Schwager SM, et al. The clinical phenotype of wild-type, heterozygous, and homozygous JAK2V617F in polycythemia vera. Cancer 2006; 106:631-5.
18. James C, Delhommeau F, Marzac C, et al. Detection of JAK2 V617F as a first intention diagnostic test for erythrocytosis. Leukemia 2006; 20:350-3.
19. Tefferi A, Strand JJ, Lasho TL, et al. Bone marrow JAK2V617F allele burden and clinical correlates in polycythemia vera. Leukemia 2007; 21:2074-5.
20. Antonioli E, Guglielmelli P, Pancrazzi A, et al. Clinical implications of the JAK2 V617F mutation in essential thrombocythemia. Leukemia 2005; 19:1847-9.
21. Campbell PJ, Scott LM, Buck G, et al. Definition of subtypes of essential throm-bocythaemia and relation to polycythaemia vera based on JAK2 V617F mutation status: a prospective study. Lancet 2005; 366:1945-53.
22. Wolanskyj AP, Lasho TL, Schwager SM, et al. JAK2 mutation in essential throm-bocythaemia: clinical associations and long-term prognostic relevance. Br J Haematol 2005; 131:208-13.
23. Kittur J, Knudson RA, Lasho TL, et al. Clinical correlates of JAK2V617F allele burden in essential thrombocythemia. Cancer 2007; 109:2279-84.
24. Tefferi A, Lasho TL, Schwager SM, et al. The JAK2 tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates. Br J Haematol 2005; 131:320-8.
25. Steensma DP, McClure RF, Karp JE, et al. JAK2V617F is a rare finding in de novo acute myeloid leukemia, but STAT3 activation is common and remains unexplained. Leukemia 2006; 20:971-8.
26. Nishii K, Nanbu R, Lorenzo VF, et al. Expression of the JAK2 V617F mutation is not found in de novo AML and MDS but is detected in MDS-derived leukemia of megakaryoblastic nature. Leukemia 2007; 21:1337-8.
27. Steensma DP, Dewald GW, Lasho TL, et al. The JAK2 V617F activating tyrosine kinase mutation is an infrequent event in both "atypical" myeloproliferative disorders and myelodysplastic syndromes. Blood 2005; 106:1207-9.
28. Fiorini A, Farina G, Reddiconto G, et al. Screening of JAK2 V617F mutation in multiple myeloma. Leukemia 2006; 20:1912-3.
29. Melzner I, Weniger MA, Menz CK, Moller P. Absence of the JAK2 V617F activating mutation in classical Hodgkin lymphoma and primary mediastinal B-cell lymphoma. Leukemia 2006; 20:157-8.
30. Tefferi A, Vardiman JW. The diagnostic interface between histology and molecular tests in myeloproliferative disorders. Curr Opin Hematol 2007; 14:115-22.
31. Tefferi A. JAK and MPL mutations in myeloid malignancies. Leuk Lymphoma 2008; 49:388-97.
32. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005; 365:1054-61.
33. Zhao R, Xing S, Li Z, et al. Identification of an acquired JAK2 mutation in polycythemia vera. J Biol Chem 2005; 280:22788-92.
34. Tiedt R, Hao-Shen H, Sobas MA, et al. Ratio of mutant JAK2-V617F to wild-type Jak2 determines the MPD phenotypes in transgenic mice. Blood 2008; 111:3931-40.
35. 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; 107:4274-81.
36. 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; 108:2435-7.
37. Kralovics R, Teo SS, Li S, et al. Acquisition of the V617F mutation ofJAK2 is a late genetic event in a subset of patients with myeloproliferative disorders. Blood 2006; 108:1377-80.
38. Pardanani A, Lasho TL, Finke C, et al. Extending Jak2V617F and MplW515 mutation analysis to single hematopoietic colonies and B and T lymphocytes. Stem Cells 2007; 25:2358-62.
39. Pardanani A, Fridley BL, Lasho TL, Gilliland DG, Tefferi A. Host genetic variation contributes to phenotypic diversity in myeloproliferative disorders. Blood 2008; 111:2785-9.
40. Jones AV, Silver RT, Waghorn K, et al. Minimal molecular response in polycythemia vera patients treated with imatinib or interferon alpha. Blood 2006; 107: 3339-41.
41. Kilpivaara O, Mukherjee S, Schram AM, et al. A germline JAK2 SNP is associated with predisposition to the development of JAK2 (V617F)-positive myeloproliferative neoplasms. Nat Genet 2009; 41:455-9.
42. Olcaydu D, Harutyunyan A, Jager R, et al. A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet 2009; 41:450-4.
43. Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A. Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 2008; 22:1299-307.
44. Passamonti F, Rumi E, Pietra D, et al. Relation between JAK2 (V617F) mutation status, granulocyte activation and constitutive mobilization of CD34-positive cells into peripheral blood in myeloproliferative disorders. Blood 2006; 107:3676-82.
45. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Clinical profile of homozygous JAK2 617V
46. Tefferi A, Lasho TL, Huang J, et al. Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival. Leukemia 2008; 22: 756-61.
47. Guglielmelli P, Barosi G, Specchia G, et al. Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 2009; 114:1477-83.
48. Pietra D, Li S, Brisci A, et al. Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 2008; 111:1686-9.
49. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007; 356:459-68.
50. Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinico-pathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007; 21:1960-3.
51. Passamonti F, Schnittger S, Girodon F, et al. Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations: a European Multicenter Study. ASH Annual Meeting Abstracts. November 20, 2009 2009; 114:3904-.
52. Lu X, Levine R, Tong W, et al. Expression of a homodimeric type I cytokine receptor is required for JAK2V617F-mediated transformation. Proc Natl Acad Sci USA 2005; 102:18962-7.
53. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3:e270
54. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472-6.
55. Chaligne R, James C, Tonetti C, et al. Evidence for MPL W515L/K mutations in hematopoietic stem cells in primitive myelofibrosis. Blood 2007; 110:3735-43.
56. Pardanani A, Lasho TL, Finke C, Markovic SN, Tefferi A. Demonstration of MPLW515K, but not JAK2V617F, in in vitro expanded CD4+ T lymphocytes. Leukemia 2007; 21:2206-7.
57. Vannucchi AM, Antonioli E, Guglielmelli P, et al. Characteristics and clinical correlates of MPL 515W
58. Beer PA, Campbell PJ, Scott LM, et al. MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 2008; 112:141-9.
59. Guglielmelli P, Pancrazzi A, Bergamaschi G, et al. Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol 2007; 137:244-7.
60. Viguie F, Aboura A, Bouscary D, et al. Common 4q24 deletion in four cases of hematopoietic malignancy: early stem cell involvement? Leukemia 2005; 19: 1411-5.
61. Delhommeau F, Dupont S, Della Valle V, et al. Mutation in TET2 in myeloid cancers. N Engl J Med 2009;360:2289-301.
62. Tefferi A, Pardanani A, Lim KH, et al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 2009;23:905-11.
63. Tefferi A, Levine RL, Lim KH, et al. Frequent TET2 mutations in systemic mastocytosis: clinical, KITD816V and FIP1L1-PDGFRA correlates. Leukemia 2009; 23:900-4.
64. Tefferi A, Lim KH, Abdel-Wahab O, et al. Detection of mutant TET2 in myeloid malignancies other than myeloproliferative neoplasms: CMML, MDS, MDS/MPN and AML. Leukemia 2009; 23:1343-5.
65. Pardanani A, Patnaik MM, Lasho TL, et al. Recurrent IDH mutations in high-risk myelodysplastic syndrome or acute myeloid leukemia with isolated del (5q). Leukemia 2010; 24:1370-2.
66. Gelsi-Boyer V, Trouplin V, Adelaide J, et al. Mutations of polycomb-associated gene ASXL1 in myelodysplastic syndromes and chronic myelomonocytic leukaemia. Br J Haematol 2009; 145:788-800.
67. Tefferi A, Lasho TL, 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; 24:1302-9.
68. Grand FH, Hidalgo-Curtis CE, Ernst T, et al. Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009; 113:6182-92.
69. Jager R, Gisslinger H, Passamonti F, et al. Deletions of the transcription factor Ikaros in myeloproliferative neoplasms. Leukemia 2010; 24:1290-8.
70. Oh ST, Simonds EF, Jones C, et al. Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 2010; 116:988-92.
71. Tefferi A, Thiele J, Orazi A, et al. Proposals and rationale for revision of the World Health Organization diagnostic criteria for polycythemia vera, essential thrombo-cythemia, and primary myelofibrosis: recommendations from an ad hoc international expert panel. Blood 2007; 110:1092-7.
72. Messinezy M, Westwood NB, El-Hemaidi I, Marsden JT, Sherwood RS, Pearson TC. Serum erythropoietin values in erythrocytoses and in primary thrombocythaemia. Br J Haematol 2002; 117:47-53.
73. Mossuz P, Girodon F, Donnard M, et al. Diagnostic value of serum erythropoietin level in patients with absolute erythrocytosis. Haematologica 2004; 89:1194-8.
74. Thiele J, Kvasnicka HM. Diagnostic impact of bone marrow histopathology in polycythemia vera (PV). Histol Histopathol 2005; 20:317-28.
75. Kvasnicka HM, Thiele J. Classification of Ph-negative chronic myeloprolifer-ative disorders: morphology as the yardstick of classification. Pathobiology 2007; 74:63-71.
76. Tefferi A, Vardiman JW. Classification and diagnosis of myeloproliferative neoplasms: the 2008 World Health Organization criteria and point-of-care diagnostic algorithms. Leukemia 2008; 22:14-22.
77. Tefferi A, Skoda R, Vardiman JW. Myeloproliferative neoplasms: contemporary diagnosis using histology and genetics. Nat Rev 2009; 6:627-37.
78. Thiele J, Kvasnicka HM, Zankovich R, Diehl V. Relevance of bone marrow features in the differential diagnosis between essential thrombocythemia and early stage idiopathic myelofibrosis. Haematologica 2000; 85:1126-34.
79. Wilkins BS, Erber WN, Bareford D, et al. Bone marrow pathology in essential thrombocythemia: interobserver reliability and utility for identifying disease subtypes. Blood 2008; 111:60-70.
80. Michiels JJ, Thiele J. Clinical and pathological criteria for the diagnosis of essential thrombocythemia, polycythemia vera, and idiopathic myelofibrosis (agnogenic myeloid metaplasia). Int J Hematol 2002; 76:133-45.
81. Barosi G, Mesa RA, Thiele J, et al. Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia 2008; 22:437-8.
82. Finazzi G, Barbui T. Evidence and expertise in the management of polycythemia vera and essential thrombocythemia. Leukemia 2008; 22:1494-502.
83. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 2009; 113:2895-901.
84. Passamonti F, Rumi E, Arcaini L, et al. Prognostic factors for thrombosis, myelo-fibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica 2008; 93:1645-51.
85. Passamonti F, Rumi E, Pungolino E, et al. Life expectancy and prognostic factors for survival in patients with polycythemia vera and essential thrombocythemia. Am J Med 2004; 117:755-61.
86. Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A. Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol 2007; 138:354-8.
87. Di Nisio M, Barbui T, Di Gennaro L, et al. The haematocrit and platelet target in polycythemia vera. Br J Haematol 2007; 136:249-59.
88. Tartaglia AP, Goldberg JD, Berk PD, Wasserman LR. Adverse effects of antiag-gregating platelet therapy in the treatment of polycythemia vera. Semin Hematol 1986; 23:172-6.
89. Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004; 350:114-24.
90. Budde U, Scharf RE, Franke P, Hartmann-Budde K, Dent J, Ruggeri ZM. Elevated platelet count as a cause of abnormal von Willebrand factor multimer distribution in plasma. Blood 1993; 82:1749-57.
91. Berk PD, Wasserman LR, Fruchtman SM, Goldberg JD. Treatment of polycythemia vera: a summary of clinical trials conducted by the polycythemia vera study group. In: Wasserman LR, Berk PD, Berlin NI, eds. Polycythemia Vera and the Myeloproliferative Disorders. Philadelphia, PA: WB Saunders; 1995: 166-94.
92. Ricksten A, Palmqvist L, Johansson P, Andreasson B. Rapid decline in JAK2V617F levels during hydroxyurea treatment in patients with polycythemia vera and essential thrombocythemia. Haematologica 2008;93:1260-1.
93. Girodon F, Schaeffer C, Cleyrat C, et al. Frequent reduction or absence of detection of the JAK-2 mutated clone in JAK2V617F-positive patients within the first years of hydroxyurea therapy. Haematologica 2008;93:1723-7.
94. Theocharides A, Passweg J, M. M, et al. The allele burden of JAK2 mutations remains stable over several years in patients with myeloproliferative disorders. Haematologica 2008;93:1890-3.
95. Thomas DJ, du Boulay GH, Marshall J, et al. Cerebral blood-flow in polycythaemia. Lancet 1977; II:161-3.
96. Pearson TC, Wetherley-Mein G. Vascular occlusive episodes and venous haema-tocrit in primary proliferative polycythaemia. Lancet 1978; II: 1219-22.
97. Tefferi A, Passamonti F. Essential thrombocythemia and pregnancy: observations from recent studies and management recommendations. Am J Hematol 2009; 84:629-30.
98. van Genderen PJ, Mulder PG, Waleboer M, van de Moesdijk D, Michiels JJ. Prevention and treatment of thrombotic complications in essential thrombocyth-aemia: efficacy and safety of aspirin. Br J Haematol 1997; 97:179-84.
99. Landolfi R, Marchioli R. European collaboration on low-dose aspirin in polycy-themia vera (ECLAP): a randomized trial. Semin Thromb Hemost 1997; 23:473-8.
100. Cortelazzo S, Finazzi G, Ruggeri M, et al. Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 1995; 332:1132-6.
101. Harrison CN, Campbell PJ, Buck G, et al. Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 2005; 353:33-45.
102. Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera. An analysis of 1, 638 patients enrolled in a prospective observational study. Blood 2005; 105:2664-70.
103. Gangat N, Wolanskyj AP, McClure RF, et al. Risk stratification for survival and leukemic transformation in essential thrombocythemia: a single institutional study of 605 patients. Leukemia 2007; 21:270-6.
104. Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood 1997; 90:3370-7.
105. Messinezy M, Pearson TC, Prochazka A, Wetherley-Mein G. Treatment of primary proliferative polycythaemia by venesection and low dose busulphan: retrospective study from one centre. Br J Haematol 1985; 61:657-66.
106. Shvidel L, Sigler E, Haran M, et al. Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia. Leukemia 2007; 21:2071-2.
107. Quintas-Cardama A, Kantarjian H, Manshouri T, et al. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 2009; 27:5418-24.
108. Kiladjian JJ, Cassinat B, Chevret S, et al. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 2008; 112:3065-72.
109. Dingli D, Schwager SM, Mesa RA, Li CY, Dewald GW, Tefferi A. Presence of unfavorable cytogenetic abnormalities is the strongest predictor of poor survival in secondary myelofibrosis. Cancer 2006; 106:1985-9.
110. Passamonti F, Rumi E, Caramella M, et al. A dynamic prognostic model to predict survival in post-polycythemia vera myelofibrosis. Blood 2008; 111:3383-7.
111. Cervantes F, Mesa R, Barosi G. New and old treatment modalities in primary myelofibrosis. Cancer J 2007; 13:377-83.
112. Elliott MA, Mesa RA, Li CY, et al. Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol 2002; 117:288-96.
113. Thomas DA, Giles FJ, Albitar M, et al. Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer 2006; 106:1974-84.
114. Tefferi A, Cortes J, Verstovsek S, et al. Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 2006; 108:1158-64.
115. Huang J, Tefferi A. Erythropoiesis stimulating agents have limited therapeutic activity in transfusion-dependent patients with primary myelofibrosis regardless of serum erythropoietin level. Eur J Haematol 2009; 83:154-5.
116. Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA. Lena-lidomide therapy in del (5) (q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia 2007; 21:1827-8.
117. Mishchenko E, Tefferi A. Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. Eur J Haematol.
118. Pardanani AD, Gotlib JR, Jamieson C, et al. A Phase I evaluation of TG101348, a selective JAK2 inhibitor, in myelofibrosis: clinical response is accompanied by significant reduction in JAK2V617F allele burden. ASH Annual Meeting Abstracts 2009; 114:755-.
119. Verstovsek S, Kantarjian H, Mesa RA, et al. Long-term follow up and optimized dosing regimen of INCB018424 in patients with myelofibrosis: durable clinical, functional and symptomatic responses with improved hematological safety. ASH Annual Meeting Abstracts 2009; 114:756-.
120. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of INCB018424, an oral, selective JAK1/JAK2 inhibitor, in patients with advanced polycythemia vera (PV) and essential thrombocythemia (ET) refractory to hydroxyurea. ASH Annual Meeting Abstracts 2009; 114:311-.
121. Verstovsek S, Kantarjian HM, Pardanani AD, et al. The JAK inhibitor, INCB018424, demonstrates durable and marked clinical responses in primary myelofibrosis (PMF) and post-polycythemia/essential thrombocythemia myelofi-brosis (post PV/ETMF). ASH Annual Meeting Abstracts 2008; 112:1762-.
122. Verstovsek S. Therapeutic potential of Janus-activated kinase-2 inhibitors for the management of myelofibrosis. Clin Cancer Res 2010; 16:1988-96.
123. Verstovsek S. Theraputic potential of JAK2 inhibitors. Hematology Am Soc Hema-tol Educ Program 2009:639-42.
124. Guardiola P, Esperou H, Cazals-Hatem D, et al. Allogeneic bone marrow transplantation for agnogenic myeloid metaplasia. French Society of Bone Marrow Transplantation. Br J Haematol 1997; 98:1004-9.
125. Daly A, Song K, Nevill T, et al. Stem cell transplantation for myelofibrosis: areport from two Canadian centers. Bone Marrow Transplant 2003; 32:35-40.
126. Kerbauy DM, Gooley TA, Sale GE, et al. Hematopoietic cell transplantation as curative therapy for idiopathic myelofibrosis, advanced polycythemia vera, and essential thrombocythemia. Biol Blood Marrow Transplant 2007; 13:355-65.
127. Ballen KK, Shrestha S, Sobocinski KA, et al. Outcome of transplantation for myelofibrosis. Biol Blood Marrow Transplant 2010; 16:358-67.
128. Kroger N, Holler E, Kobbe G, et al. Allogeneic stem cell transplantation after reduced-intensity conditioning in patients with myelofibrosis: a prospective, mul-ticenter study of the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Blood 2009; 114:5264-70.