Methylation status of c-myc oncogene in leukemic cells: hypomethylation in acute leukemia derived from myelodysplastic syndromes.

DNA methylation plays an important role in gene regulation. We have analyzed the methylation status of CCGG sites in and around the human proto-oncogene c-myc in blood cells from patients with acute and chronic leukemias and with myelodysplastic syndromes using restriction endonucleases. The 5' region of c-myc was unequivocally hypomethylated in all the 58 specimens studied, including 10 from normal bone marrow and 1 from human placenta. In contrast, the 3' region was hypermethylated in a great majority of cases. However, this region was hypomethylated in 1 of 12 patients with de novo acute myeloid leukemia, 1 of 6 patients with chronic myeloid leukemia, and 4 of 5 patients with acute myeloid leukemia preceded by a documented stage of myelodysplastic syndromes. One possible mechanism for the 3' region of c-myc to have remained hypomethylated may be a "delayed methylation" during transforming events toward a more aggressive stage of the disease, but the precise mechanism is unknown.