Is there a role for JAK inhibitors in BCR-ABL1-negative myeloproliferative neoplasms other than myelofibrosis?

Leukemia and Lymphoma

Volumn 55, Issue 12, 2014, Pages 2706-2711

  Pardanani, Animesh ^a   Tefferi, Ayalew ^a  

^a MAYO CLINIC   (United States)

Author keywords

Chronic neutrophilic leukemia; Essential thrombocythemia; JAK2; JAK2V617F; Polycythemia vera; Tyrosine kinase inhibitor

Indexed keywords

BCR ABL PROTEIN; BCR ABL1 PROTEIN; HYDROXYUREA; JANUS KINASE; JANUS KINASE 2; JANUS KINASE INHIBITOR; RUXOLITINIB; STAT PROTEIN; UNCLASSIFIED DRUG; BCR-ABL1 FUSION PROTEIN, HUMAN; COLONY STIMULATING FACTOR RECEPTOR; CSF3R PROTEIN, HUMAN; ONCOPROTEIN; PROTEIN KINASE INHIBITOR;

ARTICLE; CANCER CHEMOTHERAPY; CANCER PATIENT; CHRONIC NEUTROPHILIC LEUKEMIA; FEASIBILITY STUDY; HEMATOCRIT; HEMATOLOGIC MALIGNANCY; HUMAN; MYELOFIBROSIS; MYELOPROLIFERATIVE NEOPLASM; POLYCYTHEMIA VERA; SIGNAL TRANSDUCTION; SPLEEN SIZE; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETICS; METABOLISM; MUTATION; MYELOPROLIFERATIVE DISORDERS; PRIMARY MYELOFIBROSIS; TREATMENT OUTCOME;

FUSION PROTEINS, BCR-ABL; HUMANS; JANUS KINASE 2; JANUS KINASES; MUTATION; MYELOPROLIFERATIVE DISORDERS; ONCOGENE PROTEINS, FUSION; POLYCYTHEMIA VERA; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS; RECEPTORS, COLONY-STIMULATING FACTOR; SIGNAL TRANSDUCTION; STAT TRANSCRIPTION FACTORS; TREATMENT OUTCOME;

EID: 84919448281     PISSN: 10428194     EISSN: 10292403     Source Type: Journal    
DOI: 10.3109/10428194.2014.985159     Document Type: Article

References (63)

1. Rampal R, Al-Shahrour F, Abdel-Wahab O, et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood 2014; 123:e123-133.
2. 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.
3. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelof brosis with myeloid metaplasia. PLoS Med 2006;3:e270.
4. Pardanani AD, Levine RL, Lasho T, et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006;108:3472-3476.
5. Scott LM, Tong W, Levine RL, et al. JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 2007;356:459-468.
6. Pardanani A, Lasho TL, Finke C, Hanson CA, Teferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007;21:1960-1963.
7. 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;116:988-992.
8. Lasho TL, Pardanani A, Teferi A. LNK mutations in JAK2 mutation-negative erythrocytosis. N Engl J Med 2010; 363: 1189-1190.
9. Grand FH, Hidalgo-Curtis CE, Ernst T, et al. Frequent CBLmutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 2009;113:6182-6192.
10. Klampf T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. The New England journal of medicine 2013; 369: 2379-2390.
11. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine 2013;369:2391-2405.
12. Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3Rmutations in chronic neutrophilic leukemia and atypical CML. The New England journal of medicine 2013; 368: 1781-1790.
13. Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly prevalent and Specific mutation in chronic neutrophilic leukemia. Leukemia 2013.
14. Teferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly-annotated essential thrombocythemia, polycythemia vera and myelofbrosis. Blood 2014:e-pub ahead of print 18 July 2014; DOI: 2010.1182/blood-2014-2005-579136.
15. Teferi A. Primary myelof brosis: 2014 update on diagnosis, risk-stratification, and management. American journal of hematology 2014;89:915-925.
16. Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofbrosis. N Engl J Med 2010;363:1117-1127.
17. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelof brosis. N Engl J Med 2012;366:799-807.
18. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelof brosis. N Engl J Med 2012;366:787-798.
19. Jakaf (Ruxolitinib) label. http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/202192lbl.pdf.
20. Pardanani A, Teferi A. definition and Management of Ruxolitinib Treatment Failure in Myelofbrosis. Blood cancer journal 2014; In Press.
21. Theferi A, Rumi E, Finazzi G, et al. Survival and prognosis among 1545 patients with contemporary polycythemia vera: an international study. Leukemia 2013; 27: 1874-1881.
22. Vardiman JW, Tiele 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;114:937-951.
23. Marchioli R, Finazzi G, Landolf R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. Journal of clinical oncology: of cial journal of the American Society of Clinical Oncology 2005;23:2224-2232.
24. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. The New England journal of medicine 2013; 368: 22-33.
25. Landolf R, Marchioli R, Kutti J, et al. efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004;350:114-124.
26. Teferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. American journal of hematology 2013; 88: 507-516.
27. Barbui T, Barosi G, Birgegard G, et al. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet. Journal of clinical oncology: of cial journal of the American Society of Clinical Oncology 2011;29:761-770.
28. 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, editors. Polycythemia Vera ad the Myeloproliferative Disorders. Philadelphia: W.B. Saunders Company; 1995. p 166-194.
29. Berk PD, Goldberg JD, Silverstein MN, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. The New England journal of medicine 1981;304:441-447.
30. Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. Journal of clinical oncology: of cial journal of the American Society of Clinical Oncology 2011;29:3907-3913.
31. Finazzi G, Caruso V, Marchioli R, et al. Acute leukemia in polycythemia vera: an analysis of 1638 patients enrolled in a prospective observational study. Blood 2005;105:2664-2670.
32. Kiladjian JJ, Chomienne C, Fenaux P. Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia 2008;22: 1990-1998.
33. 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;27:5418-5424.
34. 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: 3065-3072.
35. Barosi G, Birgegard G, Finazzi G, et al. Aunified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelof brosis: results of a European LeukemiaNet (ELN) consensus process. British journal of haematology 2010;148:961-963.
36. Antonioli E, Guglielmelli P, Pieri L, et al. Hydroxyurea-related toxicity in 3, 411 patients with Ph '-negative MPN. American journal of hematology 2012;87:552-554.
37. 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.
38. Verner E, Forsyth C, Grigg A. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea. Leukemia & lymphoma 2014; 55:1139-1143.
39. Verstovsek S, Passamonti F, Rambaldi A, et al. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer 2014;120:513-520.
40. Verstovsek S, Kiladijan JJ, Griesshammer M, et al. Results of a prospective, randomized, open-label phase 3 study of ruxolitinib (RUX) in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU): the RESPONSE trial. J Clin Oncol 2014; 32:suppl; abstr 7026.
41. Barosi G, Birgegard G, Finazzi G, et al. Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference. Blood 2009;113:4829-4833.
42. Alvarez-Larran A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clini-cohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012;119:1363-1369.
43. Carobbio A, Finazzi G, Antonioli E, et al. Hydroxyurea in essential thrombocythemia: rate and clinical relevance of responses by European LeukemiaNet criteria. Blood 2010;116:1051-1055.
44. Barosi G, Teferi A, Barbui T. Do current response criteria in classical Ph-negative myeloproliferative neoplasms capture benefit for patients? Leukemia 2012;26:1148-1149.
45. Barosi G, Mesa R, Finazzi G, et al. Revised response criteria for polycythemia vera and essential thrombocythemia: a ELN and IWG-MRT consensus project. Blood 2013.
46. Reiter A, Walz C, Watmore A, et al. The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. Cancer research 2005;65:2662-2667.
47. Bousquet M, Quelen C, De Mas V, 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.
48. Dargent JL, Mathieux V, Vidrequin S, Deghorain X, Vannuf el P, Rack K. Pathology of the bone marrow and spleen in a case of myelodysplastic/myeloproliferative neoplasm associated with t(8;9) (p22;p24) involving PCM1 and JAK2 genes. European journal of haematology 2011;86:87-90.
49. Murati A, Gelsi-Boyer V, Adelaide J, et al. PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. Leukemia 2005;19:1692-1696.
50. Griesinger F, Hennig H, Hillmer F, et al. A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia. Genes, chromosomes & cancer 2005; 44: 329-333.
51. Schwaab J, Knut M, Haferlach C, et al. Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes. Annals of hematology 2014.
52. Ho JM, Beattie BK, Squire JA, Frank DA, Barber DL. Fusion of the ets transcription factor TEL to Jak2 results in constitutive Jak-Stat signaling. Blood 1999;93:4354-4364.
53. Peeters P, Raynaud SD, Cools J, 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.
54. Tzankov A, Heiss S. Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) transtocation-reply. Human pathology 2006; 37: 500-502.
55. Lierman E, Selleslag D, Smits S, Billiet J, Vandenberghe P. R uxolitinib inhibits transforming JAK2 fusion proteins in vitro and induces complete cytogenetic remission in t(8;9)(p22;p24)/PCM1-JAK2-positive chronic eosinophilic leukemia. Blood 2012;120: 1529-1531.
56. Chase A, Bryant C, Score J, et al. Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements. Haematologica 2013;98:404-408.
57. Rumi E, Milosevic JD, Casetti I, et al. efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. Journal of clinical oncology: of cial journal of the American Society of Clinical Oncology 2013;31:e269-271.
58. Gotlib J, Maxson JE, George TI, Tyner JW. The new genetics of chronic neutrophilic leukemia and atypical CML: implications for diagnosis and treatment. Blood 2013;122:1707-1711.
59. Elliott MA, Tferi A. Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management. American journal of hematology 2014;89:651-658.
60. Fleischman AG, Maxson JE, Luty SB, et al. The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood 2013; 122: 3628-3631.
61. Dao KH, Solti MB, Maxson JE, et al. Signif cant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia. Leukemia research reports 2014;3:67-69.
62. Lasho TL, Mims A, Elliott MA, Finke C, Pardanani A, Teferi A. Chronic neutrophilic leukemia with concurrent CSF3R and SETBP1 mutations: single colony clonality studies, in vitro sensitivity to JAK inhibitors and lack of treatment response to ruxolitinib. Leukemia 2014;28:1363-1365.
63. Meggendorfer M, Haferlach T, Alpermann T, et al. Specific molecular mutation patterns delineate chronic neutrophilic leukemia, atypical chronic myeloid leukemia, and chronic myelomonocytic leukemia. Haematologica 2014.