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Bortezomib therapy in myelofibrosis: a phase II clinical trial

Leukemia volume 22, pages 1636–1638 (2008)Cite this article

Myelofibrosis is an intramedullary reactive phenomenon, characteristic of the life-threatening myeloproliferative neoplasm of primary myelofibrosis (PMF).1 Clinically indistinguishable from PMF are the advanced phases of both polycythemia vera (PV) and essential thrombocythemia (ET), in which myelofibrosis is also present (post-PV and post-ET myelofibrosis, respectively (post-PV/ET MF)).1 Patients with PMF (or post-ET/PV MF) have a progressive decline marked by progressive cytopenias, extramedullary hematopoiesis (manifesting as splenomegaly and/or hepatomegaly), significant constitutional symptoms, potential for blastic transformation and premature death.2 Medical therapy for these patients has been disappointing, with clinical benefit being best categorized as palliative with only cosmetic improvements in anemia, splenomegaly or constitutional symptoms seen.2 Allogeneic stem cell transplantation can be utilized; however, a minority of patients remain appropriate candidates because of non-relapse morbidity and mortality, advanced age at diagnosis, comorbidities or lack of a suitable donor.2

The urgent need for improved therapeutic options for myelofibrosis patients has fueled scientific investigation into the pathogenetic origins of the disorder in the hope of increasing efficacy through targeted therapy. PMF has been demonstrated to be a stem cell disorder, leading to a clonal myeloproliferation.3 Origins of the clonal drive are incompletely understood, but are likely, at least in part, secondary to the recently described mutations in the activation of the JAK–STAT pathway by either the JAK2V617F and/or the MPLW515L/K mutations, which lead to downstream activation of cellular proliferation.3 In aggregate, these mutations are present in about 50–65% of patients with PMF and post-ET MF, and the majority (V617F only) in post-PV MF. Therapeutic targeting of these latter mutations are currently undergoing initial clinical testing with intriguing results.4 Prior to the targeting of myeloproliferative neoplasm-associated mutations in cell signaling, therapeutic efforts for myelofibrosis focused on targeting the reactive myelofibrosis in the hope of therapeutic gain.

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Authors and Affiliations

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

    R A Mesa, A Pardanani, K Hussein, T Lasho, W Wu & A Tefferi

  2. Department of Leukemia, MD Anderson Cancer Center, University of Texas, Houston, TX, USA

    S Verstovsek

  3. Division of Leukemia Mayo Clinic Jacksonville, Jacksonville, FL, USA

    C Rivera

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  1. R A Mesa
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  2. S Verstovsek
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  3. C Rivera
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  4. A Pardanani
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  6. T Lasho
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  7. W Wu
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  8. A Tefferi
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Correspondence to R A Mesa.

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Mesa, R., Verstovsek, S., Rivera, C. et al. Bortezomib therapy in myelofibrosis: a phase II clinical trial. Leukemia 22, 1636–1638 (2008). https://doi.org/10.1038/leu.2008.32

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