P15^INK4b Gene Methylation and Myelodysplastic Syndromes

Abstract

Myelodysplastic syndromes (MDS) are clonal disorders, which frequently undergo leukemic transformation. It was recently shown that the promoter of the p15 ^INK4b but not the p 16^INK4a gene is frequently and selectively hypermethylated in MDS. The p15^INK4b gene is a cyclin dependent kinase inhibitor gene, which is actively transcribed after TGFβ exposure. Methylation of the p15^INK4b gene is significantly correlated with blastic bone marrow involvement, and sequential analyses have shown that methylation increases with disease evolution toward AML. These data strongly suggest that p15^INK4b 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 TGFβ remains to be investigated.

Key Words:

• methylation
• MDS
• Cell cycle
• P15^INK4b
• TGFβ