p15(INK4b) gene methylation and myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are clonal disorders, which frequently unde rgo leukemia transformation. It was recently shown that the promoter of the p15(INK4b) but not the p16(INK4a) gene is frequently and selectively hyper methylated in MDS, The p15(INK4b) gene is a cyclin dependent kinase inhibit or gene, which is actively transcribed after TGF beta exposure. Methylation of the p15(INK4b) gene is significantly correlated with blastic bone marro w involvement, and sequential analyses have shown that methylation increase s with disease evolution toward AML. These data strongly suggest that p15(I NK4b) gene methylation is a mechanism allowing leukemic cells to escape to inhibitory signals from the bone marrow environment, however the exact role of p15(INK4b) gene methylation in disruption of the signal mediated by TGF beta remains to be investigated.