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

References

• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A. Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 2007;21:1960–1963.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Lasho TL, Pardanani A, Tefferi A. LNK mutations in JAK2 mutation-negative erythrocytosis. N Engl J Med 2010;363:1189–1190.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. The New England journal of medicine 2013;369:2379–2390.
   PubMed Web of Science ®Google Scholar
• Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. The New England journal of medicine2013;369:2391–2405.
   Web of Science ®Google Scholar
• Maxson JE, Gotlib J, Pollyea DA, et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. The New England journal of medicine 2013;368:1781–1790.
   PubMed Web of Science ®Google Scholar
• Pardanani A, Lasho TL, Laborde RR, et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia 2013.
   Web of Science ®Google Scholar
• Tefferi A, Guglielmelli P, Larson DR, et al. Long-term survival and blast transformation in molecularly-annotated essential thrombocythemia, polycythemia vera and myelofibrosis. Blood 2014:e-pub ahead of print 18 July 2014; DOI: 2010.1182/blood- 2014-2005-579136.
   Web of Science ®Google Scholar
• Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. American journal of hematology 2014;89:915–925.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117–1127.
   PubMed Web of Science ®Google Scholar
• Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012;366:799–807.
   PubMed Web of Science ®Google Scholar
• Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012;366:787–798.
   PubMed Web of Science ®Google Scholar
• Jakafi (Ruxolitinib) label. http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/202192lbl.pdf.
   Google Scholar
• Pardanani A, Tefferi A. Definition and Management of Ruxolitinib Treatment Failure in Myelofibrosis. Blood cancer journal 2014; In Press.
   Google Scholar
• Tefferi 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.
   PubMed Web of Science ®Google Scholar
• 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;114:937–951.
   PubMed Web of Science ®Google Scholar
• Marchioli R, Finazzi G, Landolfi R, et al. Vascular and neoplastic risk in a large cohort of patients with polycythemia vera. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2005;23:2224–2232.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Landolfi R, Marchioli R, Kutti J, et al. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 2004;350:114–124.
   PubMed Web of Science ®Google Scholar
• Tefferi A. Polycythemia vera and essential thrombocythemia: 2013 update on diagnosis, risk-stratification, and management. American journal of hematology 2013;88:507–516.
   PubMedGoogle Scholar
• 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 : official journal of the American Society of Clinical Oncology 2011;29:761–770.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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 : official journal of the American Society of Clinical Oncology 2011;29:3907–3913.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Kiladjian JJ, Chomienne C, Fenaux P. Interferon-alpha therapy in bcr-abl-negative myeloproliferative neoplasms. Leukemia 2008;22: 1990–1998.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Barosi G, Birgegard G, Finazzi G, et al. A unified definition of clinical resistance and intolerance to hydroxycarbamide in polycythaemia vera and primary myelofibrosis: results of a European LeukemiaNet (ELN) consensus process. British journal of haematology 2010;148:961–963.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Alvarez-Larran A, Pereira A, Cervantes F, et al. Assessment and prognostic value of the European LeukemiaNet criteria for clinicohematologic response, resistance, and intolerance to hydroxyurea in polycythemia vera. Blood 2012;119:1363–1369.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Barosi G, Tefferi A, Barbui T. Do current response criteria in classical Ph-negative myeloproliferative neoplasms capture benefit for patients? Leukemia 2012;26:1148–1149.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Dargent JL, Mathieux V, Vidrequin S, Deghorain X, Vannuffel 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Tzankov A, Heiss S. Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) transtocation - reply. Human pathology 2006;37: 500–502.
   PubMed Web of Science ®Google Scholar
• Lierman E, Selleslag D, Smits S, Billiet J, Vandenberghe P. Ruxolitinib 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.
   PubMed Web of Science ®Google Scholar
• Chase A, Bryant C, Score J, et al. Ruxolitinib as potential targeted therapy for patients with JAK2 rearrangements. Haematologica 2013;98:404–408.
   Google Scholar
• 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 : official journal of the American Society of Clinical Oncology 2013;31:e269–271.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Elliott MA, Tefferi A. Chronic neutrophilic leukemia 2014: Update on diagnosis, molecular genetics, and management. American journal of hematology 2014;89:651–658.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Dao KH, Solti MB, Maxson JE, et al. Significant clinical response to JAK1/2 inhibition in a patient with CSF3R-T618I-positive atypical chronic myeloid leukemia. Leukemia research reports 2014;3:67–69.
   PubMedGoogle Scholar
• Lasho TL, Mims A, Elliott MA, Finke C, Pardanani A, Tefferi 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar