Identification of a novel methylated gene as a prognostic factor in hematological malignancies and its clinical application.

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Bone morphogenetic proteins (BMP) are multifunctional regulators of cell proliferation and apoptosis in various types of malignant cells. In this study, we investigated BMP-6 promoter methylation in patients with various types of leukemias. The BMP-6 methylation was found preferentially in adult T-cell leukemia (ATL) compared with other types of leukemias. Among subtypes of ATL, the BMP-6 gene was more frequently methylated in aggressive ATL forms of acute and lymphoma types than less malignant chronic ATL and smoldering ATL. Serial analysis demonstrated an increasing methylation of CpG sites in the BMP-6 promoter and the resultant suppression of BMP-6 expression as ATL progressed. These findings suggested that BMP-6 promoter methylation is likely to be a common epigenetic event at later stages of ATL and that the methylation profiles may be useful for the staging of ATL as well as for evaluation of the individual risk of developing the disease.