Mutations in CCAAT/enhancer binding protein α (CEBPA) are seen in 5% to 14% of acute myeloid leukemia (AML) and have been associated with a favorable clinical outcome. Most AMLs with CEBPA mutations simultaneously carry 2 mutations (CEBPAdouble-mut), usually biallelic, whereas 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 (28 CEBPAdouble-mut and 13 CEBPA single-mut cases) CEBPAdouble-mut associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multi-variable analysis that included cytoge-netic risk, FZT3-ITD and NPM1 mutation, white blood cell count, and age. In contrast, CEBPA single-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.

CCAAT enhancer binding protein alpha, CD135 antigen, acute granulocytic leukemia, age, article, cancer survival, controlled study, cytogenetics, denaturing high performance liquid chromatography, disease marker, gene expression profiling, gene mutation, genetic heterogeneity, genetic risk, human, human cell, leukocyte count, messenger RNA, nucleophosmin, nucleotide sequence, priority journal, prognosis,
Erasmus MC: University Medical Center Rotterdam

Wouters, B.J, Löwenberg, B, Erpelinck, C.A.J, van Putten, W.L.J, Valk, P.J.M, & Delwel, H.R. (2009). Double CEBPA mutations, but not single CEBPA mutations, define a subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood, 113(13), 3088–3091. doi:10.1182/blood-2008-09-179895