Clearing the path for MPN therapy monitoring

In this issue of Blood, Takahashi and colleagues have helped clarify the validity of using peripheral blood for monitoring the JAK2-V617F allele burden among the myeloproliferative neoplasms.1 The understanding of the BCR-ABL-negative MPNs of essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) encountered a true watershed in 2005 with the discovery of the JAK2 V617F mutation.2 This latter discovery had an incredible impact on many levels, inspiring the hematology research community to investigate the pathophysiology of these MPNs as well as begin development of new MPNdirected therapies. Subsequently, multiple additional mutations in the molecular pathways that can be involved with the pathophysiology of MPNs include the JAK2 Exon 12; mutations in MPL, ASXL1, IDH1/2, EZH2; and deletions in TET2.3 Although many of these additional molecular and genetic discoveries may have important implications in terms of the behavior of subsets of myeloproliferative neoplasia of MPNs, they may have prognostic implications particular to the area of leukemic transformation, but most of these remain relatively low-prevalence mutations; now almost 9 years after the discovery of the JAK2 V617F, this mutation remains by far the most prevalent, widely tested, and impactful of the MPN mutations.