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Novel Therapies for Myelofibrosis

  • Myeloproliferative Neoplasms (B Stein, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The purpose of the review was to provide a contemporary update of novel agents and targets under investigation in myelofibrosis in the Janus kinase (JAK) inhibitor era.

Recent Findings

Myelofibrosis (MF) is a clonal stem cell disease characterized by marrow fibrosis and a heterogeneous disease phenotype with a variable degree of splenomegaly, cytopenias, and constitutional symptoms that significantly impact quality of life and survival. Overactive JAK/STAT signaling is a hallmark of MF. The only approved therapy for MF, JAK1/2 inhibitor ruxolitinib, can ameliorate splenomegaly, improve symptoms, and prolong survival in some patients. Therapeutic challenges remain, however. Myelosuppression limits the use of ruxolitinib in some patients, eventual drug resistance is common, and the underlying malignant clone persists despite therapy. A deeper understanding of the pathogenesis of MF has informed the development of additional agents.

Summary

Promising targets under investigation include JAK1 and JAK2 and downstream intermediates in related signaling pathways, epigenetic modifiers, pro-inflammatory cytokines, and immune regulators.

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Acknowledgements

KP was supported by the National Institutes of Health/National Institute of General Medical Sciences Clinical Therapeutics grant (T32 GM007019).

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  1. Section of Hematology/Oncology, Department of Medicine, The University of Chicago, 5841 S. Maryland Ave, MC2115, Chicago, IL, 60637, USA

    Kristen Pettit & Olatoyosi Odenike

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Kristen Pettit declares no potential conflicts of interest.

Olatoyosi Odenike declares membership on advisory boards within the past 2 years: Incyte, CTI/Baxalta, Jazz Pharmaceuticals, Pfizer, Celgene, and consulting fees from ABBVIE.

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This article is part of the Topical Collection on Myeloproliferative Neoplasms

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Pettit, K., Odenike, O. Novel Therapies for Myelofibrosis. Curr Hematol Malig Rep 12, 611–624 (2017). https://doi.org/10.1007/s11899-017-0403-0

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