Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features Academic Article uri icon

Overview

MeSH Major

  • CCAAT-Enhancer-Binding Proteins
  • DNA Methylation
  • DNA, Neoplasm
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Leukemia, Myeloid, Acute

abstract

  • 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 studies revealed that these 2 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 compared with normal CD34(+) hematopoietic cells, whereas CEBPA mutant cases showed only mild changes in DNA methylation compared with these normal progenitors. Biologically, CEBPA-silenced leukemias presented with a decreased response to myeloid growth factors in vitro.

publication date

  • March 19, 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2945920

Digital Object Identifier (DOI)

  • 10.1182/blood-2008-08-172387

PubMed ID

  • 19168792

Additional Document Info

start page

  • 2795

end page

  • 804

volume

  • 113

number

  • 12