Genetics of the myeloproliferative neoplasms

Since the discovery of the JAK2V617F mutation in 2005, an increasing number of somatic and germline genetic events responsible for myeloproliferative neoplasm (MPN) pathogenesis have been uncovered. The purpose of this review is to outline the most recent discoveries of the genetic alterations found in patients with MPNs.

In addition to the JAK2V617F mutation, additional mutations in the JAK–STAT pathway have been discovered including a series of mutations in exon 12 of JAK2, the thrombopoietic receptor gene MPL, and in the gene encoding the JAK–STAT inhibitory adaptor protein LNK. Additionally, mutations in genes which appear to affect the epigenome of MPN patients have been discovered including mutations in TET2, IDH1/ 2, EZH2, and ASXL1. Lastly, some insights into the genetic events which contribute to transformation of a chronic MPN phenotype to acute myeloid leukemia have been elucidated, including deletion of the transcription factor Ikaros.

The spectrum of genetic abnormalities found in the classic MPNs has increased over the last 6 years and somatic mutations in JAK2, MPL, LNK, TET2, EZH2, ASXL1, and IDH1/2 have all been described. Despite this, the initiating genetic events responsible for the development of MPNs is still not totally understood.