E-GEOD-14479 - Transcription profiling by array of human lymphoblasts from patients with acute myeloid lymphoma or T acute lymphoblastic leukemia, mutant for CEBPA
Released on 24 January 2009, last updated on 27 April 2012
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. Experiment Overall Design: Direct comparison of gene expression 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, and with 9 samples of T Acute Lymphoblastic Leukemia (T-ALL) patients.
transcription profiling by array, unknown experiment type
Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features. Figueroa ME, Wouters BJ, Skrabanek L, Glass J, Li Y, Erpelinck-Verschueren CA, Langerak AW, Löwenberg B, Fazzari M, Greally JM, Valk PJ, Melnick A, Delwel R. , Europe PMC 19168792