Genotype-phenotype interactions in the myeloproliferative neoplasms

Abstract

The chronic myeloproliferative neoplasms (MPNs) are clonal disorders characterized by overproduction of mature myeloid cells. They share associations with molecular abnormalities such as the JAK2V617F mutation but are distinguished by important phenotypic differences. This review first considers the factors that may influence phenotype in JAK2-mutated MPNs, especially polycythemia vera (PV) and essential thrombocythemia (ET), and then discusses the mutations implicated in JAK2-negative MPNs such as in MPL and epigenetic regulators. Current evidence supports a model where ET and PV are disorders of relatively low genetic complexity, whereas evolution to myelofibrosis or blast-phase disease reflects accumulation of a higher mutation burden.