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Novel myelofibrosis treatment strategies: potential partners for combination therapies

Leukemia volume 28, pages 2139–2147 (2014)Cite this article

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Abstract

Of the myeloproliferative neoplasms (MPNs), myelofibrosis (MF) is associated with the greatest symptom burden and poorest prognosis and is characterized by constitutional symptoms, cytopenias, splenomegaly and bone marrow fibrosis. A hallmark of MF is dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway that has led to the development of JAK inhibitors targeting this pathway. Calreticulin gene mutations have recently been identified in JAK2 mutation-negative patients with MF. Identification of JAK inhibitor resistance and broad contributions to MF disease pathogenesis from epigenetic deregulators, pathways that work in concert with JAK/STAT (that is, mammalian target of rapamycin/AKT/phosphoinositide 3-kinase, RAS/RAF/MEK, PIM kinase), fibrosis-promoting factors and the MF megakaryocyte, suggest that numerous options may be partnered with a JAK inhibitor. Therefore, we will discuss logical and potential partners for combination therapies for the treatment of patients with MF.

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Acknowledgements

Financial support for medical assistance was provided by Novartis Pharmaceuticals. We thank Daniel Hutta and Matthew Hoelzle for their medical editorial assistance with this manuscript.

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  1. Northwestern University Feinberg School of Medicine, Chicago, IL, USA

    B L Stein

  2. Northwestern Medicine Developmental Therapeutics Institute, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

    B L Stein & F Giles

  3. Division of Hematology/Oncology, Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, FL, USA

    R Swords

  4. Klinik für Innere Medizin II, Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

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BLS was previously a member of Speakers Bureau, Incyte Corporation and has participated in Advisory Boards for Incyte Corporation and Sanofi Oncology. RS has declared no conflict of interest. AH has received honoraria and research funding from Novartis, Bristol-Myers Squibb and Pfizer; and FG has received honoraria and research funding from Novartis.

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Stein, B., Swords, R., Hochhaus, A. et al. Novel myelofibrosis treatment strategies: potential partners for combination therapies. Leukemia 28, 2139–2147 (2014). https://doi.org/10.1038/leu.2014.176

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  • DOI: https://doi.org/10.1038/leu.2014.176

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