Transcriptomics

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Genome-wide DNA methylation in CEBPA mutant and CEBPA silenced AML


ABSTRACT: Acute Myeloid Leukemia (AML) is a heterogeneous disease from the molecular and biological standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients that shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, while the rest presented with silencing of this gene and co-expression of certain T cell markers. DNA methylation studies revealed that these two groups of patients could be readily segregated in an unsupervised fashion based on their DNA methylation profiles alone. Furthermore, CEBPA silencing was associated with the presence of an aberrant DNA hypermethylation signature, which was not present in the CEBPA mutant group. This aberrant hypermethylation occurred more frequently at sites within CpG islands. CEBPA silenced leukemias also displayed marked hypermethylation when compared with normal CD34+ hematopoietic cells, while CEBPA mutant cases showed only mild changes in DNA methylation when compared to these normal progenitors. Biologically, CEBPA silenced leukemias presented with a decreased response to myeloid growth factors in vitro. Keywords: DNA methylation profiling Direct comparison of DNA methylation in leukemic blasts from 8 patients with Acute Myeloid Leukemia (AML) carrying a CEBPA mutation and 8 patients with AML without CEBPA mutation but with silencing of CEBPA expression. Two control groups are included: 8 CD34+ bone marrow samples from healthy donors and 9 samples of T Acute Lymphoblastic Leukemia (T-ALL) patients.

ORGANISM(S): Homo sapiens  

SUBMITTER: Ruud Delwel   Maria Eugenia Figueroa  Maria E Figueroa  Bas J Wouters  Ari Melnick 

PROVIDER: E-GEOD-14417 | ArrayExpress | 2010-05-07

SECONDARY ACCESSION(S): GSE14417PRJNA111499

REPOSITORIES: GEO, ArrayExpress

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Publications

Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features.

Figueroa Maria E ME   Wouters Bas J BJ   Skrabanek Lucy L   Glass Jacob J   Li Yushan Y   Erpelinck-Verschueren Claudia A J CA   Langerak Anton W AW   Löwenberg Bob B   Fazzari Melissa M   Greally John M JM   Valk Peter J M PJ   Melnick Ari A   Delwel Ruud R  

Blood 20090123 12


Acute myeloid leukemia is a heterogeneous disease from the molecular and biologic standpoints, and even patients with a specific gene expression profile may present clinical and molecular heterogeneity. We studied the epigenetic profiles of a cohort of patients who shared a common gene expression profile but differed in that only half of them harbored mutations of the CEBPA locus, whereas the rest presented with silencing of this gene and coexpression of certain T-cell markers. DNA methylation s  ...[more]

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