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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.

Abstract：

: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.

journal_name

Blood

journal_title

Blood

authors

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

doi

10.1182/blood-2008-09-179895

subject

Has Abstract

pub_date

2009-03-26 00:00:00

pages

3088-91

issue

13

eissn

0006-4971

issn

1528-0020

pii

blood-2008-09-179895

journal_volume

113

pub_type

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