Mutations in myeloproliferative neoplasms – their significance and clinical use

ABSTRACT

Introduction: Clonal hematologic diseases of the blood such as polycythemia vera, essential thrombocythemia and primary myelofibrosis belong to the BCR-ABL negative Myeloproliferative Neoplasms (MPN). These diseases are characterized by clonal expansion of hematopoietic precursor cells followed by increased production of differentiated cells of the myeloid lineage. Initiation of clonal hematopoiesis, formation of a clinical phenotype as well as disease progression form part of MPN disease evolution. The disease is driven by acquired somatic mutations in critical pathways such as cytokine signaling, epigenetic regulation, RNA splicing, and transcription factor signaling.

Areas covered: The following review aims to provide an overview of the mutational landscape of MPN, the impact of these mutations in MPN pathogenesis as well as their prognostic value. Finally, a summary of how these mutations are being used or could potentially be used for the treatment of MPN patients is presented.

Expert commentary: The genetic landscape of MPN patients has been successfully dissected within the past years with the advent of new sequencing technologies. Integrating the genetic information within a clinical setting is already benefitting patients in terms of disease monitoring and prognostic information of disease progression but will be further intensified within the next years.

KEYWORDS:

• Essential thromobocythemia
• myeloproliferative neoplasms
• polycythemia vera
• primary myelofibrosis
• treatment

Declaration of interest

R Kralovics is on the advisory board for Novartis, and PharmaEssentia, and has received speaker honoraria from PharmaEssentia and AOP Orphan Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was supported by the Austrian Science Fund (FWF4702-B20).