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

作者：Wouters Bas J; Lowenberg Bob; Erpelinck Verschueren Claudia A J; van Putten Wim L J; Valk Peter J M; Delwel Ruud^*

来源：Blood, 2009, 113(13): 3088-3091.

DOI：10.1182/blood-2008-09-179895

Mutations in CCAAT/enhancer binding protein alpha (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 (CEBPA(double-mut)), usually biallelic, whereas single heterozygous mutations (CEBPA(single-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 CEBPA(double-mut) and 13 CEBPA(single-mut) cases). CEBPA(double-mut) associated with a unique gene expression profile as well as favorable overall and event-free survival, retained in multi-variable analysis that included cytogenetic risk, FLT3-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. ( Blood. 2009; 113: 3088-3091)

• 出版日期2009-3-26