Aberrant methylation in promoter-associated CpG islands of multiple genes in chronic myelogenous leukemia blast crisis

Abstract

Chronic myelogenous leukemia (CML) has a typical progressive course with transition from a chronic phase to a terminal blast crisis phase. The mechanisms that lead to disease progression remain to be elucidated. To understand the role of aberrant methylation in the progression of CML, DNA methylation patterns in 16 patients with CML blast crisis were analyzed. Methylation status was analyzed by methylation-specific PCR (MSP) for 13 genes, including cell cycle regulating genes, DNA repair genes, apoptosis-related genes, a differentiation- associated gene and a cytokine signaling gene. The frequency of samples with methylation in each of the following genes were: p15, 18%; MGMT, 12%; RARβ, 12%; p16, 6%; DAPK, 6% and FHIT, 6%. In total, four (25%) cases showed methylation of at least one gene. None of the 16 cases showed hypermethylation of the hMLH1 or hMSH2 genes. These results suggest that hypermethylation of cell cycle control genes, but not DNA mismatch repair genes, play a significant role in the progression of CML.