Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features
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.
|Keywords||CCAAT enhancer binding protein alpha, CD34 antibody, CpG island, DNA, DNA methylation, acute granulocytic leukemia, acute leukemia, adult, article, cancer patient, cell marker, clinical article, clinical feature, cohort analysis, controlled study, epigenetics, gene expression profiling, gene locus, gene mutation, gene silencing, genome analysis, growth factor, hematopoietic cell, human, human cell, in vitro study, leukemogenesis, lymphatic leukemia, myeloid leukemia, phenotype, priority journal|
|Persistent URL||dx.doi.org/10.1182/blood-2008-08-172387, hdl.handle.net/1765/16250|
Figueroa, M.E., Wouters, B.J., Skrabanek, L., Glass, J., Li, Y., Erpelinck, C.A.J., … Delwel, H.R.. (2009). Genome-wide epigenetic analysis delineates a biologically distinct immature acute leukemia with myeloid/T-lymphoid features. Blood, 113(12), 2795–2804. doi:10.1182/blood-2008-08-172387