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Heterogeneity within AML with CEBPA mutations; only CEBPA double mutations, but not single CEBPA mutations are associated with favourable prognosis.

ABSTRACT: CCAAT/enhancer binding protein alpha (CEBPA) mutations in AML are associated with favourable prognosis and are divided into N- and C-terminal mutations. The majority of AML patients have both types of mutations. We assessed the prognostic significance of single (n=7) and double (n=12) CEBPA mutations among 224 AML patients. Double CEBPA mutations conferred a decisively favourable overall (P=0.006) and disease-free survival (P=0.013). However, clinical outcome of patients with single CEBPA mutations was not different from CEBPA wild-type patients. In a multivariable analysis, only double -- but not single -- CEBPA mutations were identified as independent prognostic factors. These findings indicate heterogeneity within AML patients with CEBPA mutations.

SUBMITTER: Pabst T

PROVIDER: S-EPMC2676545 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Genetic heterogeneity of cytogenetically normal AML with mutations of <i>CEBPA</i>.

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Transcription profiling of human newly diagnosed AML CEBPA double and single mutant and CEBPA wild type AML.

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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.

Project description: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 multivariable 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.

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2011-08-04 | GSE22845 | GEO

CSF3R mutations have a high degree of overlap with CEBPA mutations in pediatric AML.

Project description: Not available

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

2009-01-21 | GSE14468 | GEO

Allele-specific expression of GATA2 due to epigenetic dysregulation in CEBPA double-mutant AML.

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