Genomic heterogeneity in myeloproliferative neoplasms and applications to clinical practice

Abstract

The myeloproliferative neoplasms (MPN) polycythaemia vera, essential thrombocythaemia and primary myelofibrosis are chronic myeloid disorders associated most often with mutations in JAK2, MPL and CALR, and in some patients with additional acquired genomic lesions. Whilst the molecular mechanisms downstream of these mutations are now clearer, it is apparent that clinical phenotype in MPN is a product of complex interactions, acting between individual mutations, between disease subclones, and between the tumour and background host factors. In this review we first discuss MPN phenotypic driver mutations and the factors that interact with them to influence phenotype. We consider the importance of ongoing studies of clonal haematopoiesis, which may inform a better understanding of why MPN develop in specific individuals. We then consider how best to deploy genomic testing in a clinical environment and the challenges as well as opportunities that may arise from more routine, comprehensive genomic analysis of patients with MPN.

Keywords: Essential thrombocythaemia; Genomics; Myelofibrosis; Myeloproliferative; Polycythaemia vera; Prognosis.