The role of different genetic subtypes of CEBPA mutated AML.
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.
MLL Munich Leukemia Laboratory, Munich, Germany.
A
A
Fasan
MLL Munich Leukemia Laboratory, Munich, Germany.
C
C
Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany.
T
T
Alpermann
MLL Munich Leukemia Laboratory, Munich, Germany.
S
S
Jeromin
MLL Munich Leukemia Laboratory, Munich, Germany.
V
V
Grossmann
MLL Munich Leukemia Laboratory, Munich, Germany.
C
C
Eder
MLL Munich Leukemia Laboratory, Munich, Germany.
S
S
Weissmann
MLL Munich Leukemia Laboratory, Munich, Germany.
F
F
Dicker
MLL Munich Leukemia Laboratory, Munich, Germany.
A
A
Kohlmann
MLL Munich Leukemia Laboratory, Munich, Germany.
S
S
Schindela
MLL Munich Leukemia Laboratory, Munich, Germany.
W
W
Kern
MLL Munich Leukemia Laboratory, Munich, Germany.
T
T
Haferlach
MLL Munich Leukemia Laboratory, Munich, Germany.
S
S
Schnittger
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D015470:Leukemia, Myeloid, Acute / Q000145:classification / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D011379:Prognosis; D051941:fms-Like Tyrosine Kinase 3 / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C000716967:NPM1 protein, human; D000090243:Nucleophosmin; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3