TitleGenome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features.
Publication TypeJournal Article
Year of Publication2009
AuthorsFigueroa, Maria E., Wouters Bas J., Skrabanek Lucy, Glass Jacob, Li Yushan, Erpelinck-Verschueren Claudia A. J., Langerak Anton W., Löwenberg Bob, Fazzari Melissa, Greally John M., Valk Peter J. M., Melnick Ari, and Delwel Ruud
Date Published2009 Mar 19
KeywordsAdolescent, Adult, CCAAT-Enhancer-Binding Proteins, Cohort Studies, CpG Islands, DNA Methylation, DNA, Neoplasm, Drug Resistance, Neoplasm, Gene Expression Profiling, Gene Expression Regulation, Leukemic, Gene Regulatory Networks, Gene Silencing, Granulocyte Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, Interleukin-3, Leukemia, Myeloid, Acute, Male, Middle Aged, Neoplasm Proteins, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Tumor Cells, Cultured

<p>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.</p>

Alternate JournalBlood
PubMed ID19168792
PubMed Central IDPMC2945920
Grant ListGM007288 / GM / NIGMS NIH HHS / United States
R01 CA118316 / CA / NCI NIH HHS / United States
CA118316 / CA / NCI NIH HHS / United States
T32 GM007288 / GM / NIGMS NIH HHS / United States
R01 HD044078 / HD / NICHD NIH HHS / United States
R01 CA104348 / CA / NCI NIH HHS / United States