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Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group
Author(s) -
Rotunno Giada,
Pacilli Annalisa,
Artusi Valentina,
Rumi Elisa,
Maffioli Margherita,
Delaini Federica,
Brogi Giada,
Fanelli Tiziana,
Pancrazzi Alessandro,
Pietra Daniela,
Bernardis Isabella,
Belotti Clara,
Pieri Lisa,
Sant'Antonio Emanuela,
Salmoiraghi Silvia,
Cilloni Daniela,
Rambaldi Alessandro,
Passamonti Francesco,
Barbui Tiziano,
Manfredini Rossella,
Cazzola Mario,
Tagliafico Enrico,
Vannucchi Alessandro M.,
Guglielmelli Paola
Publication year - 2016
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.24377
Subject(s) - essential thrombocythemia , myelofibrosis , medicine , polycythemia vera , oncology , mutation , clinical significance , allele , idh1 , genotyping , genetics , genotype , biology , gene , bone marrow
Transformation to secondary myelofibrosis (MF) occurs as part of the natural history of polycythemia vera (PPV‐MF) and essential thrombocythemia (PET‐MF). Although primary (PMF) and secondary MF are considered similar diseases and managed similarly, there are few studies specifically focused on the latter. The aim of this study was to characterize the mutation landscape, and describe the main clinical correlates and prognostic implications of mutations, in a series of 359 patients with PPV‐MF and PET‐MF. Compared with PV and ET, the JAK2 V617F and CALR mutated allele burden was significantly higher in PPV‐MF and/or PET‐MF, indicating a role for accumulation of mutated alleles in the process of transformation to MF. However, neither the allele burden nor the type of driver mutation influenced overall survival (OS), while absence of any driver mutation (triple negativity) was associated with significant reduction of OS in PET‐MF, similar to PMF. Of the five interrogated subclonal mutations ( ASXL1, EZH2, SRSF2, IDH1, and IDH2 ), that comprise a prognostically detrimental high molecular risk (HMR) category in PMF, only SRSF2 mutations were associated with reduced survival in PET‐MF, and no additional mutation profile with prognostic relevance was highlighted. Overall, these data indicate that the molecular landscape of secondary forms of MF is different from PMF, suggesting that unknown mutational events might contribute to the progression from chronic phase disease to myelofibrosis. These findings also support more extended genotyping approaches aimed at identifying novel molecular abnormalities with prognostic relevance for patients with PPV‐MF and PET‐MF. Am. J. Hematol. 91:681–686, 2016. © 2016 Wiley Periodicals, Inc.