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Underlying mechanisms of the JAK2V617F mutation in the pathogenesis of myeloproliferative neoplasms

Grundlegende Mechanismen der JAK2V617F-Mutation bei der Pathogenese myeloproliferativer Neoplasien

  • Hauptreferate: Hämatopathologie
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Abstract

Chronic myeloproliferative neoplasms (MPN) comprise a spectrum of clonal neoplastic disorders characterized by overproduction of terminally differentiated cells of the myeloid lineage. A common genetic basis for the BCR-ABL-negative MPN disorders was elucidated in 2005 with the identification of the JAK2V617F mutation in the majority of MPN patients. The discovery of JAK2V617F had a dramatic impact on the diagnosis and treatment of MPN. Testing for JAK2 mutations is now included in the World Health Organization (WHO) criteria for the diagnosis of MPN, and in 2011 the oral JAK2 kinase inhibitor ruxolitinib became the first Food and Drug Administration (FDA)-approved drug for the treatment of myelofibrosis. The drug is now also approved in Europe and Canada.

Zusammenfassung

Zu den chronischen myeloproliferativen Neoplasien (MPN) gehört ein Spektrum klonaler neoplastischer Erkrankungen, die durch Überproduktion terminal differenzierter Zellen der myeloischen Reihe gekennzeichnet sind. Eine gemeinsame genetische Grundlage der BCR-ABL-negativen MPN wurde 2005 mit der Identifizierung der JAK2V617F-Mutation bei der Mehrzahl der MPN-Patienten nachgewiesen. Die Entdeckung von JAK2V617F hatte drastische Auswirkungen auf die Diagnose und Therapie von MPN. Die Untersuchung auf JAK2-Mutationen ist nun Bestandteil der Kriterien der Weltgesundheitsorganisation (WHO) für die Diagnose von MPN, und 2011 erhielt der JAK2-Kinase-Inhibitor Ruxolitinib als erstes Medikament die Zulassung der Food and Drug Administration (FDA) zur Behandlung der Myelofibrose. Das Medikament ist mittlerweile ebenfalls in Europa und Kanada zugelassen.

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Authors and Affiliations

  1. Division of Hematology, Brigham and Women’s Hospital, Harvard Medical School, 02115, Boston, MA, USA

    A. Mullally MD

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  1. A. Mullally MD
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Correspondence to A. Mullally MD.

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A. Mullally states that she has no competing interest.

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

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Mullally, A. Underlying mechanisms of the JAK2V617F mutation in the pathogenesis of myeloproliferative neoplasms. Pathologe 37 (Suppl 2), 175–179 (2016). https://doi.org/10.1007/s00292-016-0240-2

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  • DOI: https://doi.org/10.1007/s00292-016-0240-2

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