Abnormal expression of friend leukemia virus integration 1 protein is an adverse prognostic factor in acute myeloid leukemia
Menée sur 511 patients atteints d'une leucémie myéloïde aiguë nouvellement diagnostiquée, cette étude montre qu'un niveau d'expression anormal de la protéine FLI1, un membre de la famille des facteurs de transcription ETS, est associé à un pronostic défavorable
Friend leukemia virus integration 1 (FLI1), an Ets transcription factor family member, is linked to AML by chromosomal events at the FLI1 locus, but the biological impact of FLI1 expression on AML is unknown. FLI1 protein expression was measured in 511 newly diagnosed AML patients. Expression was similar in blood and marrow and higher at diagnosis than relapse (p= .02). Compared to normal CD34+ cells, expression in AML was above/below normal in 32% and 5% of cases. Levels correlated negatively with an antecedent hematologic disorder (p=0.002) but not with age, or cytogenetics. Mutated NPM1 (p=0.0007) or FLT3-ITD (p< 0.02) had higher expression. FLI1 levels correlated negatively with 10 (of 195) proteins associated with proliferation and stromal interaction and positively (R >0.3) with 19 others. FLI1 level was not predictive of remission attainment, but, those with low or high FLI1 expression had shorter remission duration (22.6 and 40.3 vs. 51.1 weeks, P= 0.01) and overall survival (45.2 and 35.4 vs. 59.4 weeks, p=0.03). High FLI1 levels were adverse in univariate and multivariate analysis. FLI1 expression is frequently abnormal and prognostically adverse in AML. FLI1 and/or its response genes may be therapeutically targetable to interfere with AML cell biology.
Blood , résumé, 2011