DNA Methylation profiling of chronic myelogenous leukemia in relationship to genomic translocation

To determine the effects of a specific chromosomal lesion, the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer, we compared DNA methylation of 1,505 selected promoter CpGs in Chronic Myelogenous Leukemia (CML), Acute Lymphoblastic Leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34 + hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR- ABL (Acute Promyelocytic Leukemia (APL) and Gastrointestinal Stromal Tumors (GIST)). In this study, the DNA methylation profile of CML was more closely related to APL, another myeloid leukemia, than Ph + ALL. Although DNA methylation profiles were consistent within a specific tumor type, overall DNA methylation profiles were not influenced by BCR-ABL gene translocation in the cancers and tissues studied. We conclude that DNA methylation profiles may reflect the cell of origin in cancers rather than the chromosomal lesions involved in leukemogenesis.