Gene expression profiling of CEBPA double and single mutant and CEBPA wild type AML.

Mutations in CCAAT/enhancer binding protein alpha (CEBPA) are seen in 5-14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry two mutations (CEBPAdouble-mut), usually biallelic, while single heterozygous mutations (CEBPAsingle-mut) are less frequently seen. Using denaturing high performance liquid chromatography and nucleotide sequencing we identified among a cohort of 598 newly diagnosed AMLs a subset of 41 CEBPA mutant cases, i.e. 28 CEBPAdouble-mut and 13 CEBPAsingle-mut cases. CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multivariable analysis that included cytogenetic risk, FLT3-ITD and NPM1 mutation, white blood cell count and age. In contrast, CEBPAsingle-mut AMLs did not express a discriminating signature and could not be distinguished from wild type cases as regards clinical outcome. These results demonstrate significant underlying heterogeneity within CEBPA mutation positive AML with prognostic relevance.

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Wouters BJ, Löwenberg B, Erpelinck-Verschueren CA, van Putten WL, Valk PJ, Delwel R