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Status |
Public on Jan 15, 2009 |
Title |
Genome-wide DNA methylation in CEBPA mutant and CEBPA silenced AML |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by genome tiling array
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Summary |
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
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Overall design |
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.
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Contributor(s) |
Figueroa ME, Wouters BJ, Melnick A, Delwel R |
Citation(s) |
19168792 |
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Submission date |
Jan 14, 2009 |
Last update date |
Mar 20, 2012 |
Contact name |
Maria Eugenia Figueroa |
E-mail(s) |
mef162@miami.edu
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Organization name |
University of Miiami
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Department |
Human Genetics
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Lab |
Maria Figueroa
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Street address |
1501 NW 10th Ave, BRB 709A, Locator code C227
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City |
Miami |
State/province |
FL |
ZIP/Postal code |
33136 |
Country |
USA |
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Platforms (1) |
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Samples (33)
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Relations |
BioProject |
PRJNA111499 |