Skip to main content
SpringerLink
Log in

A Critical Review of the Role and Limitations of JAK Inhibitors in Myelofibrosis Therapy

  • Chapter
  • First Online:
Myeloproliferative Neoplasms

Part of the book series: Hematologic Malignancies ((HEMATOLOGIC))

  • 1017 Accesses

Abstract

The discovery of JAK2V617F has rejuvenated interest in JAK-STAT, both as an oncogenic pathway and a drug target in BCR-ABL1-negative myeloproliferative neoplasms (MPN). While the majority of MPN patients harbor gain-of-function JAK2 or MPL mutations, the complex clonal structure of these diseases and presence of additional mutations undermine the likelihood that JAK inhibitor therapy in MPN will replicate what has been achieved with imatinib in chronic myeloid leukemia. Most of the currently available ATP-mimetic JAK inhibitors are effective in alleviating constitutional symptoms and reducing spleen size; the dominant mode of action may be downregulation of proinflammatory cytokines through anti-JAK1 activity. In contrast, myelosuppression that contributes to both the beneficial and detrimental effects on peripheral blood counts may be anti-JAK2-mediated. Nonhematologic toxicities include gastrointestinal disturbances, asymptomatic elevation of liver and pancreatic enzymes, peripheral neuropathy, and hyperacute relapse of symptoms during treatment interruption. Identification of the best-in-class JAK inhibitor in terms of overall efficacy and toxicity profile remains a work in progress.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abdel-Wahab O, Manshouri T, Patel J, Harris K, Yao J, Hedvat C et al (2010) Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res 70:447–452

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Wahab O, Pardanani A, Rampal R, Lasho TL, Levine RL, Tefferi A (2011) DNMT3A mutational analysis in primary myelofibrosis, chronic myelomonocytic leukemia and advanced phases of myeloproliferative neoplasms. Leukemia 25:1219–1220

    Article  PubMed  CAS  Google Scholar 

  • Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M et al (2011) Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol 29:3179–3184

    Article  PubMed  Google Scholar 

  • Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S et al (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 365:1054–1061

    PubMed  CAS  Google Scholar 

  • Beer PA, Campbell PJ, Scott LM, Bench AJ, Erber WN, Bareford D et al (2008) MPL mutations in myeloproliferative disorders: analysis of the PT-1 cohort. Blood 112:141–149

    Article  PubMed  CAS  Google Scholar 

  • Carbuccia N, Murati A, Trouplin V, Brecqueville M, Adelaide J, Rey J et al (2009) Mutations of ASXL1 gene in myeloproliferative neoplasms. Leukemia 23:2183–2186

    Article  PubMed  CAS  Google Scholar 

  • Carobbio A, Thiele J, Passamonti F, Rumi E, Ruggeri M, Rodeghiero F et al (2011) Risk factors for arterial and venous thrombosis in WHO-defined essential thrombocythemia: an international study of 891 patients. Blood 117:5857–5859

    Article  PubMed  CAS  Google Scholar 

  • Cervantes F, Mesa R, Barosi G (2007) New and old treatment modalities in primary myelofibrosis. Cancer J 13:377–383

    Article  PubMed  CAS  Google Scholar 

  • Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E et al (2009) New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood 113:2895–2901

    Article  PubMed  CAS  Google Scholar 

  • Cortelazzo S, Finazzi G, Ruggeri M, Vestri O, Galli M, Rodeghiero F et al (1995) Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis. N Engl J Med 332:1132–1136

    Article  PubMed  CAS  Google Scholar 

  • De Sanctis V, Mazzucconi MG, Spadea A, Alfo M, Mancini M, Bizzoni L et al (2003) Long-term evaluation of 164 patients with essential thrombocythaemia treated with pipobroman: occurrence of leukaemic evolution. Br J Haematol 123:517–521

    Article  PubMed  Google Scholar 

  • Deeg HJ, Odenike O, Scott BL, Estrov Z, Cortes JE, Thomas DA et al (2011) Phase II study of SB1518, an orally available novel JAK2 inhibitor, in patients with myelofibrosis. J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 29(15_Suppl.):6515

    Google Scholar 

  • Delhommeau F, Dupont S, Della Valle V, James C, Trannoy S, Masse A et al (2009) Mutation in TET2 in myeloid cancers. N Engl J Med 360:2289–2301

    Article  PubMed  Google Scholar 

  • Druker BJ (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112:4808–4817

    Article  PubMed  CAS  Google Scholar 

  • Elliott MA, Mesa RA, Li CY, Hook CC, Ansell SM, Levitt RM et al (2002) Thalidomide treatment in myelofibrosis with myeloid metaplasia. Br J Haematol 117:288–296

    Article  PubMed  CAS  Google Scholar 

  • Ernst T, Chase AJ, Score J, Hidalgo-Curtis CE, Bryant C, Jones AV et al (2010) Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 42:722–726

    Article  PubMed  CAS  Google Scholar 

  • Gangat N, Strand J, Li CY, Wu W, Pardanani A, Tefferi A (2007) Leucocytosis in polycythaemia vera predicts both inferior survival and leukaemic transformation. Br J Haematol 138:354–358

    Article  PubMed  Google Scholar 

  • Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S et al (2011) DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 29:392–397

    Article  PubMed  Google Scholar 

  • Gery S, Gueller S, Chumakova K, Kawamata N, Liu L, Koeffler HP (2007) Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders. Blood 110:3360–3364

    Article  PubMed  CAS  Google Scholar 

  • Gery S, Cao Q, Gueller S, Xing H, Tefferi A, Koeffler HP (2009) Lnk inhibits myeloproliferative disorder-associated JAK2 mutant, JAK2V617F. J Leukoc Biol 85:957–965

    Article  PubMed  CAS  Google Scholar 

  • Grand FH, Hidalgo-Curtis CE, Ernst T, Zoi K, Zoi C, McGuire C et al (2009) Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms. Blood 113:6182–6192

    Article  PubMed  CAS  Google Scholar 

  • Green A, Beer P (2010) Somatic mutations of IDH1 and IDH2 in the leukemic transformation of myeloproliferative neoplasms. N Engl J Med 362:369–370

    Article  PubMed  CAS  Google Scholar 

  • Guglielmelli P, Pancrazzi A, Bergamaschi G, Rosti V, Villani L, Antonioli E et al (2007) Anaemia characterises patients with myelofibrosis harbouring Mpl mutation. Br J Haematol 137:244–247

    Article  PubMed  CAS  Google Scholar 

  • Guglielmelli P, Barosi G, Specchia G, Rambaldi A, Lo Coco F, Antonioli E et al (2009) Identification of patients with poorer survival in primary myelofibrosis based on the burden of JAK2V617F mutated allele. Blood 114:1477–1483

    Article  PubMed  CAS  Google Scholar 

  • Harrison CN, Campbell PJ, Buck G, Wheatley K, East CL, Bareford D et al (2005) Hydroxyurea compared with anagrelide in high-risk essential thrombocythemia. N Engl J Med 353:33–45

    Article  PubMed  CAS  Google Scholar 

  • Harrison CN, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman RJ, Stalbovskaya V et al (2011) Results of a randomized study of the JAK inhibitor ruxolitinib (INC424) versus best available therapy (BAT) in primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF). J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 29(18_Suppl.):LBA6501

    Google Scholar 

  • Harutyunyan A, Klampfl T, Cazzola M, Kralovics R (2011) p53 lesions in leukemic transformation. N Engl J Med 364:488–490

    Article  PubMed  CAS  Google Scholar 

  • Jager R, Gisslinger H, Passamonti F, Rumi E, Berg T, Gisslinger B et al (2010) Deletions of the transcription factor Ikaros in myeloproliferative neoplasms. Leukemia 24:1290–1298

    Article  PubMed  CAS  Google Scholar 

  • James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 434:1144–1148

    Article  PubMed  CAS  Google Scholar 

  • Jones AV, Chase A, Silver RT, Oscier D, Zoi K, Wang YL et al (2009) JAK2 haplotype is a major risk factor for the development of myeloproliferative neoplasms. Nat Genet 41:446–449

    Article  PubMed  CAS  Google Scholar 

  • Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M et al (2008) Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood 112:3065–3072

    Article  PubMed  CAS  Google Scholar 

  • Kilpivaara O, Mukherjee S, Schram AM, Wadleigh M, Mullally A, Ebert BL et al (2009) A germline JAK2 SNP is associated with predisposition to the development of JAK2(V617F)-positive myeloproliferative neoplasms. Nat Genet 41:455–459

    Article  PubMed  CAS  Google Scholar 

  • Klampfl T, Harutyunyan A, Berg T, Gisslinger B, Schalling M, Bagienski K et al (2011) Genome integrity of myeloproliferative neoplasms in chronic phase and during disease progression. Blood 118:167–176

    Article  PubMed  CAS  Google Scholar 

  • Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR et al (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med 352:1779–1790

    Article  PubMed  CAS  Google Scholar 

  • Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C et al (2004) Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med 350:114–124

    Article  PubMed  CAS  Google Scholar 

  • “Leukemia and Hematosarcoma” Cooperative Group, European Organization for Research on Treatment of Cancer (EORTC) (1981) Treatment of polycythaemia vera by radiophosphorus or busulphan: a randomized trial. Br J Cancer 44:75–80

    Google Scholar 

  • Levine RL, Wadleigh M, Cools J, Ebert BL, Wernig G, Huntly BJ et al (2005) Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell 7:387–397

    Article  PubMed  CAS  Google Scholar 

  • Loh ML, Sakai DS, Flotho C, Kang M, Fliegauf M, Archambeault S et al (2009) Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. Blood 114:1859–1863

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Trillos A, Gaya A, Maffioli M, Arellano-Rodrigo E, Calvo X, Diaz-Beya M et al (2010) Efficacy and tolerability of hydroxyurea in the treatment of the hyperproliferative manifestations of myelofibrosis: results in 40 patients. Ann Hematol 89:1233–1237

    Article  PubMed  CAS  Google Scholar 

  • Mesa RA, Niblack J, Wadleigh M, Verstovsek S, Camoriano J, Barnes S et al (2007) The burden of fatigue and quality of life in myeloproliferative disorders (MPDs): an international Internet-based survey of 1179 MPD patients. Cancer 109:68–76

    Article  PubMed  Google Scholar 

  • Mesa RA, Schwager S, Radia D, Cheville A, Hussein K, Niblack J et al (2009) The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res 33:1199–1203

    Article  PubMed  Google Scholar 

  • Mishchenko E, Tefferi A (2010) Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. Eur J Haematol 85:192–199

    Article  PubMed  CAS  Google Scholar 

  • Moliterno AR, Hexner E, Roboz GJ, Carroll M, Luger S, Mascarenhas J et al (2009) An open-label study of CEP-701 in patients with JAK2 V617F-positive PV and ET: update of 39 enrolled patients. Blood 114:Abstract 753

    Google Scholar 

  • Oh ST, Simonds EF, Jones C, Hale MB, Goltsev Y, Gibbs KD Jr et al (2010) Novel mutations in the inhibitory adaptor protein LNK drive JAK-STAT signaling in patients with myeloproliferative neoplasms. Blood 116:988–992

    Article  PubMed  CAS  Google Scholar 

  • Olcaydu D, Harutyunyan A, Jager R, Berg T, Gisslinger B, Pabinger I et al (2009) A common JAK2 haplotype confers susceptibility to myeloproliferative neoplasms. Nat Genet 41:450–454

    Article  PubMed  CAS  Google Scholar 

  • Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al (2006) MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 108:3472–3476

    Article  PubMed  CAS  Google Scholar 

  • Pardanani A, Lasho TL, Finke C, Hanson CA, Tefferi A (2007) Prevalence and clinicopathologic correlates of JAK2 exon 12 mutations in JAK2V617F-negative polycythemia vera. Leukemia 21:1960–1963

    Article  PubMed  CAS  Google Scholar 

  • Pardanani A, Lasho T, Finke C, Oh ST, Gotlib J, Tefferi A (2010a) LNK mutation studies in blast-phase myeloproliferative neoplasms, and in chronic-phase disease with TET2, IDH, JAK2 or MPL mutations. Leukemia 24:1713–1718

    Article  PubMed  CAS  Google Scholar 

  • Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM et al (2010b) Longer-term follow up with TG101348 therapy in myelofibrosis confirms sustained improvement in splenomegaly, disease-related symptoms, and JAK2V617F allele burden. ASH Annual Meeting Abstracts 116:459

    Google Scholar 

  • Pardanani A, Guglielmelli P, Lasho TL, Pancrazzi A, Finke CM, Vannucchi AM et al (2011a) Primary myelofibrosis with or without mutant MPL: comparison of survival and clinical features involving 603 patients. Leukemia. doi:101038/leu2011161

  • Pardanani A, Gotlib JR, Jamieson C, Cortes JE, Talpaz M, Stone RM et al (2011b) Safety and efficacy of TG101348, a selective JAK2 inhibitor, in myelofibrosis. J Clin Oncol 29:789–796

    Article  PubMed  CAS  Google Scholar 

  • Pardanani A, Caramazza D, George G, Lasho TL, Hogan WJ, Litzow MR et al (2011c) Safety and efficacy of CYT387, a JAK-1/2 inhibitor, for the treatment of myelofibrosis. J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 29(15_Suppl.):6514

    Google Scholar 

  • Passamonti F, Brusamolino E, Lazzarino M, Barate C, Klersy C, Orlandi E et al (2000) Efficacy of pipobroman in the treatment of polycythemia vera: long-term results in 163 patients. Haematologica 85:1011–1018

    PubMed  CAS  Google Scholar 

  • Passamonti F, Rumi E, Malabarba L, Arcaini L, Orlandi E, Brusamolino E et al (2004) Long-term follow-up of young patients with essential thrombocythemia treated with pipobroman. Ann Hematol 83:495–497

    Article  PubMed  Google Scholar 

  • Passamonti F, Rumi E, Arcaini L, Boveri E, Elena C, Pietra D et al (2008) Prognostic factors for thrombosis, myelofibrosis, and leukemia in essential thrombocythemia: a study of 605 patients. Haematologica 93:1645–1651

    Article  PubMed  Google Scholar 

  • Passamonti F, Schnittger S, Girodon F, Kiladjian J-J, McMullin MF, Ruggeri M et al (2009) Molecular and clinical features of the myeloproliferative neoplasm associated with JAK2 exon 12 mutations: a European Multicenter Study. ASH Annual Meeting Abstracts 114:3904

    Google Scholar 

  • Passamonti F, Rumi E, Pietra D, Elena C, Boveri E, Arcaini L et al (2010) A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications. Leukemia 24:1574–1579

    Article  PubMed  CAS  Google Scholar 

  • Petti MC, Spadea A, Avvisati G, Spadea T, Latagliata R, Montefusco E et al (1998) Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971–1991). Leukemia 12:869–874

    Article  PubMed  CAS  Google Scholar 

  • Pietra D, Li S, Brisci A, Passamonti F, Rumi E, Theocharides A et al (2008) Somatic mutations of JAK2 exon 12 in patients with JAK2 (V617F)-negative myeloproliferative disorders. Blood 111:1686–1689

    Article  PubMed  CAS  Google Scholar 

  • Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al (2006) MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 3:e270

    Article  PubMed  Google Scholar 

  • Quintas-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S et al (2009) Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol 27:5418–5424

    Article  PubMed  CAS  Google Scholar 

  • Santos FP, Kantarjian HM, Jain N, Manshouri T, Thomas DA, Garcia-Manero G et al (2010) Phase 2 study of CEP-701, an orally available JAK2 inhibitor, in patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis. Blood 115:1131–1136

    Article  PubMed  CAS  Google Scholar 

  • Scott LM, Tong W, Levine RL, Scott MA, Beer PA, Stratton MR et al (2007) JAK2 exon 12 mutations in polycythemia vera and idiopathic erythrocytosis. N Engl J Med 356:459–468

    Article  PubMed  CAS  Google Scholar 

  • Shvidel L, Sigler E, Haran M, Klepfish A, Duek A, Berrebi A et al (2007) Busulphan is safe and efficient treatment in elderly patients with essential thrombocythemia. Leukemia 21:2071–2072

    Article  PubMed  CAS  Google Scholar 

  • Siragusa S, Vaidya R, Tefferi A (2009) Hydroxyurea effect on marked splenomegaly associated with primary myelofibrosis: response rates and correlation with JAK2V617F allele burden. Blood (ASH Annual Meeting Abstracts) 114:Abstract 4971

    Google Scholar 

  • Tefferi A, Cortes J, Verstovsek S, Mesa RA, Thomas D, Lasho TL et al (2006) Lenalidomide therapy in myelofibrosis with myeloid metaplasia. Blood 108:1158–1164

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Lasho TL, Mesa RA, Pardanani A, Ketterling RP, Hanson CA (2007) Lenalidomide therapy in del(5)(q31)-associated myelofibrosis: cytogenetic and JAK2V617F molecular remissions. Leukemia 21:1827–1828

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Lasho TL, Huang J, Finke C, Mesa RA, Li CY et al (2008) 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 22:756–761

    Article  PubMed  CAS  Google Scholar 

  • Tefferi A, Vaidya R, Caramazza D, Finke C, Lasho T, Pardanani A (2011) Circulating interleukin (IL)-8, IL-2R, IL-12, and IL-15 levels are independently prognostic in primary myelofibrosis: a comprehensive cytokine profiling study. J Clin Oncol 29:1356–1363

    Article  PubMed  CAS  Google Scholar 

  • Thoennissen NH, Lasho T, Thoennissen GB, Ogawa S, Tefferi A, Koeffler HP (2011) Novel CUX1 missense mutation in association with 7q- at leukemic transformation of MPN. Am J Hematol 86:703–705

    Article  PubMed  CAS  Google Scholar 

  • Thomas DA, Giles FJ, Albitar M, Cortes JE, Verstovsek S, Faderl S et al (2006) Thalidomide therapy for myelofibrosis with myeloid metaplasia. Cancer 106:1974–1984

    Article  PubMed  CAS  Google Scholar 

  • Vannucchi AM, Antonioli E, Guglielmelli P, Pardanani A, Tefferi A (2008a) Clinical correlates of JAK2V617F presence or allele burden in myeloproliferative neoplasms: a critical reappraisal. Leukemia 22:1299–1307

    Article  PubMed  CAS  Google Scholar 

  • Vannucchi AM, Antonioli E, Guglielmelli P, Pancrazzi A, Guerini V, Barosi G et al (2008b) Characteristics and clinical correlates of MPL 515W>L/K mutation in essential thrombocythemia. Blood 112:844–847

    Article  PubMed  CAS  Google Scholar 

  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al (2009) The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 114:937–951

    Article  PubMed  CAS  Google Scholar 

  • Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Levine R et al (2010a) Durable responses with the JAK1/ JAK2 inhibitor, INCB018424, in patients with polycythemia vera (PV) and essential thrombocythemia (ET) refractory or intolerant to hydroxyurea (HU). Blood (ASH Annual Meeting Abstracts) 116:Abstract 313

    Google Scholar 

  • Verstovsek S, Deeg HJ, Odenike O, Zhu J, Kantarjian H, Estrov Z et al (2010b) Phase 1/2 study of SB1518, a novel JAK2/FLT3 inhibitor, in the treatment of primary myelofibrosis. ASH Annual Meeting Abstracts 116:3082

    Google Scholar 

  • Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA et al (2010c) Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 363:1117–1127

    Article  PubMed  CAS  Google Scholar 

  • Verstovsek S, Mesa RA, Gotlib JR, Levy RS, Gupta V, DiPersio JF et al (2011) Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF). J Clin Oncol, ASCO Annual Meeting Proceedings (Post-Meeting Edition) 29(15_Suppl.):6500

    Google Scholar 

Download references

Acknowledgments

I have received a research grant from the Henry J Predolin Foundation.

Conflict of Interest Statement

I am principal investigator or co-investigator on clinical trials that are supported by TargeGen, Sanofi-Aventis, Incyte, BMS, Cytopia, YM BioSciences, Celgene, and Novartis. No payments outside of clinical trial support were paid to either myself or my institution. Support for laboratory investigations relevant to the clinical trials or preclinical laboratory research has been provided by TargeGen and Cytopia.

Author information

Authors and Affiliations

  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Animesh Pardanani

Authors
  1. Animesh Pardanani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Animesh Pardanani .

Editor information

Editors and Affiliations

  1. Div. Ematologia, Ospedali Riuniti di Bergamo, Largo Barozzi 1, Bergamo, 24128, Italy

    Tiziano Barbui

  2. Dept. Internal Medicine, Div. Hematology, Mayo Clinic, First Street SW. 200, Rochester, 55905, Minnesota, USA

    Ayalew Tefferi

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Pardanani, A. (2012). A Critical Review of the Role and Limitations of JAK Inhibitors in Myelofibrosis Therapy. In: Barbui, T., Tefferi, A. (eds) Myeloproliferative Neoplasms. Hematologic Malignancies. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-24989-1_17

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-24989-1_17

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-24988-4

  • Online ISBN: 978-3-642-24989-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation