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Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations

  • Myeloproliferative Disorders (C Harrison, Section Editor)
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Abstract

During the past 10 years, major progress has been accomplished with the discovery of activating mutations that are associated with the vast majority of BCR-ABL negative human myeloproliferative neoplasms (MPNs). The identification in 2005 of JAK2 V617F triggered great interest in the JAK2-STAT5/STAT3 pathway. Discovery in 2006 of mutants of thrombopoietin receptor (TPO-R/MPL) and later on of mutants in negative regulators of JAK-STAT pathway led to the notion that persistent JAK2 activation is a hallmark of MPNs. In 2013, mutations in the gene coding for the chaperone calreticulin were reported in 20–30 % of essential thrombocythemia and primary myelofibrosis patients. Here, we will address the question: what do we know about calreticulin that could help us understand its role in MPNs? In addition to oncogenic driver mutations, certain MPNs also exhibit epigenetic mutations. Targeting of both oncogenic drivers and epigenetic defects could be required for effective therapy.

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Acknowledgments

Support from the Ludwig Institute for Cancer Research, FRS-FNRS Belgium, Programs IAP BCHM61B5, the Action de Recherche Concertée projects ARC10/15-027 and MEXP31C1, Salus Sanguinis Foundation and MPN Foundation USA is acknowledged. XC is a post-doctoral fellow of the de Duve Institute.

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Conflict of Interest

Xavier Cahu declares no potential conflicts of interest. Stefan N. Constantinescu is a board member for Dafra Pharma, Belgium, Personal Genetics, Romania, Novartis, Myelofibrosis Board, and Shire, Ad-Hoc Anagrelide; is a consultant for Novartis, Teva, and Shire; reports a grant from Aventis; and payment for the development of educational presentations including service on speakers’ bureaus and travel/accommodations expenses covered or reimbursed from Teva, Shire, and Novartis.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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  1. Ludwig Institute for Cancer Research, Avenue Hippocrate 74, UCL 75-4, Brussels, B1200, Belgium

    Xavier Cahu & Stefan N. Constantinescu

  2. de Duve Institute, Université catholique de Louvain, Brussels, B1200, Belgium

    Xavier Cahu & Stefan N. Constantinescu

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  1. Xavier Cahu
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Correspondence to Stefan N. Constantinescu.

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This article is part of the Topical Collection on Myeloproliferative Disorders

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Cahu, X., Constantinescu, S.N. Oncogenic Drivers in Myeloproliferative Neoplasms: From JAK2 to Calreticulin Mutations. Curr Hematol Malig Rep 10, 335–343 (2015). https://doi.org/10.1007/s11899-015-0278-x

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  • DOI: https://doi.org/10.1007/s11899-015-0278-x

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