EZH2 mutational status predicts poor survival in myelofibrosis
Cette étude (518 cas) montre que des mutations du gène EZH2 sont associées à un pronostic défavorable chez les patients atteints d'une myélofibrose primitive
We genotyped 370 subjects with primary myelofibrosis (PMF) and 148 with post-polycythemia vera/post-essential thrombocythemia myelofibrosis (PPV/PET-MF) for mutations of EZH2. Mutational status at diagnosis was correlated with hematological parameters, clinical manifestations and outcome. A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF and 9.4% of PET-MF patients; most were exonic heterozygous missense changes. EZH2 mutation coexisted with JAK2V617F or ASXL1 mutation in 12/29 (41.4%) and 6/27 (22.2%) evaluated patients; TET2 and CBL mutations were found in 2 and 1 subject, respectively. EZH2 mutated PMF patients had significantly higher leukocyte count, blast cell count and larger spleen at diagnosis, and most of them (52.6%) were high IPSS-risk category. After a median follow-up of 39 months, 128 patients (25.9%) died, 81 (63.3%) because of leukemia. Leukemia-free and overall survival were significantly reduced in EZH2 mutated PMF patients (P=.028 and P<.001 respectively); possibly due to low number of mutated cases, no such impact was seen for PPV/PET-MF. In multivariate analysis, survival of PMF patients was predicted by IPSS high-risk category, a <25% JAK2V617F allele burden and EZH2 mutated status. We conclude that EZH2 mutations are independently associated with shorter survival in patients with PMF.
Blood , résumé, 2011