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Molecular Pathogenesis of Myeloproliferative Neoplasms

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

Abstract

Purpose of Review

Myeloproliferative neoplasms (MPNs) are chronic hematological malignancies characterized by increased proliferation of MPN stem and myeloid progenitor cells with or without bone marrow fibrosis that typically lead to increased peripheral blood cell counts. The genetic and cytogenetic alterations that initiate and drive the development of MPNs have largely been defined, and we summarize these here.

Recent Findings

In recent years, advances in understanding the pathogenesis of MPNs have defined a long-preclinical phase in JAK2-mutant MPN, identified genetic loci associated with MPN predisposition and uncovered mechanistic insights in CALR-mutant MPN. The integration of molecular genetics into prognostic risk models is well-established in myelofibrosis and ongoing studies are interrogating the prognostic implications of concomitant mutations in ET and PV. Despite all these advances, the field is deficient in clonally selective therapies to effectively target the MPN clone at any stage of disease, from pre-clinical to advanced.

Summary

Although the biological understanding of the pathogenesis of MPNs has progressed quickly, substantial knowledge gaps remain, including in the molecular mechanisms underlying MPN progression and myelofibrotic transformation. An ongoing goal for the MPN field is to translate advances in biological understanding to improved treatments for patients.

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Acknowledgements

A.M. receives funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH) (R01HL131835), the Gabrielle’s Angel Foundation, the Leukemia & Lymphoma Society and the Starr Cancer Consortium (grant #I15-0026). B.R. receives funding from the German Cancer Aid (Mildred-Scheel scholarship, grant #70114570).

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  1. Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Harvard Institutes of Medicine Building, Room 738, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA

    Benjamin Rolles & Ann Mullally

  2. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    Ann Mullally

  3. Broad Institute, Cambridge, MA, USA

    Ann Mullally

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A.M. receives research funding from the Relay Therapeutics. A.M. has consulted for the Janssen, PharmaEssentia, Constellation, Aclaris Therapeutics, Cellarity, Morphic Therapeutics and Biomarin Pharmaceuticals. AM has received research funding from the Janssen and Actuate Therapeutics.

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Rolles, B., Mullally, A. Molecular Pathogenesis of Myeloproliferative Neoplasms. Curr Hematol Malig Rep 17, 319–329 (2022). https://doi.org/10.1007/s11899-022-00685-1

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