alexa The role of different genetic subtypes of CEBPA mutated AML.
Haematology

Haematology

Journal of Blood Disorders & Transfusion

Author(s): Fasan A, Haferlach C, Alpermann T, Jeromin S, Grossmann V, , Fasan A, Haferlach C, Alpermann T, Jeromin S, Grossmann V,

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Abstract The prognostic impact of mutations in the CCAAT/enhancer binding protein α (CEBPA) gene was evaluated in the context of concomitant molecular mutations and cytogenetic aberrations in acute myeloid leukemia (AML). CEBPA was screened in a cohort of 2296 adult AML cases. Of 244 patients (10.6\%) with CEBPA mutations, 140 cases (6.1\%) were single-mutated (CEBPAsm) and 104 cases (4.5\%) were double-mutated (CEBPAdm). Cytogenetic analysis revealed normal karyotype in 172/244 (70.5\%) of CEBPAmut cases, whereas in 72/244 cases (29.5\%) at least one cytogenetic aberration was detected. Concurrent molecular mutations were seen less frequently in CEBPAdm than in CEBPAsm AML cases (69.2\% vs 88.6\% P<0.001). In detail, the spectrum of concurrent mutations was different in both groups with the frequent occurrence of GATA1 and WT1 mutations in CEBPAdm patients. In contrast, FLT3-ITD, NPM1, ASXL1 and RUNX1 mutations were detected more frequently in CEBPAsm cases. Favorable outcome was restricted to CEBPAdm cases and remained an independent prognostic factor for a favorable outcome in multivariate analysis (hazard ratio: 0.438, P=0.020). Outcome in CEBPAsm cases strongly depended on concurrent FLT3-ITD. In conclusion, we propose that only CEBPAdm should be considered as an entity in the WHO classification of AML and should be clearly distinguished from CEBPAsm AML. This article was published in Leukemia and referenced in Journal of Blood Disorders & Transfusion

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