BACKGROUND/AIM We have yet to understand why JAK2-positive myeloproliferative neoplasms (MPN) patients manifest different phenotypes despite harboring JAK2 mutations and what drives secondary transformations.

PATIENTS AND METHODS Using targeted sequencing, we analyzed mutational status of 17 polycythemia vera (PV), 16 essential thrombocythemia (ET), 8 primary myelofibrosis (PMF) patients who tested positive for JAK by polymerase chain reaction.

RESULTS The somatic mutations in JAK2 influence the clinical behavior of the disease. We found that ASXL1 or EZH2 mutation acquisition after JAK2 leads to PV, while ASXL1 mutation acquisition before JAK2 leads to ET or PMF. Mutations in TP53, ASXL1, and splicing genes are associated with the prognosis of MPN. PMF was more frequently associated with splicing mutations, while PV was more closely related to mutations in chromatin modifiers. The presence of these mutations influenced hemogram at MPN diagnosis.

CONCLUSION Each subtype of MPN harbors distinct patterns of somatic mutations and acquisition order, while mutations in TP53, ASXL1, and splicing genes may be associated with the prognosis of MPN.