Mutation status of essential thrombocythemia and primary myelofibrosis defines clinical outcome

Mutation status of essential thrombocythemia and primary myelofibrosis defines clinical outcomeFor the majority of patients with essential thrombocythemia (ET) and primary myelofibrosis (PMF), clinical diagnosis can be aided by mutational findings in JAK2, CALR or MPL.The JAK2 V617F mutation is found in about half of the cases and has been included as a major criterion for diagnosis in the WHO 2008 classification. 1 A minor proportion has instead been reported to harbor mutations in the MPL gene.The most frequently reported mutations, W515L and W515K, have been found in up to 5% of ET and 10% of PMF patients.2 In remaining cases, mutations in exon 9 of the CALR gene have filled a substantial part of the molecular diagnostic gap.3,4 Although there is a diagnostic value of mutations in the three genes JAK2, CALR and MPL, the impact of the mutation type correlated to the clinical outcome for patients has not been fully elucidated.Reports indicate that the outcome varies with different mutations.The clinical course of patients with CALR-mutated disease seems to be more indolent with a lower risk of thrombosis in ET and better overall survival (OS) in PMF compared to JAK2 mutated patients.5 It has been suggested that myeloproliferative neoplasms (MPNs) might be diagnosed based on mutation type to better match prognosis, rather than the classical phenotypical division.6 Moreover, a small group of ET and PMF patients are triple-negative (TN), i.e. lacking any of these mutations.This indicates that mutations in other genes might be important for the development of MPN.If so, these mutations could be useful as diagnostic or prognostic markers.In this study, we searched for additional mutations in the TN group and compared the findings and clinical data to patients with mutations in JAK2, CALR or MPL, to study if gene mutations could diversify diagnosis and serve as prognostic markers.The type of mutation was found to have prognostic implications, and TN ET and PMF are uncommon but indicate inferior survival.