Prognostic impact of p15 gene aberrations in acute leukemia.

Thep15gene (also known asCDKN2B,INK4B,p15INK4B), located in band 9p21, encodes a protein that induces a G1-phase cell cycle arrest through inhibition of CDK4/6 (cyclin-dependent kinase 4/6). It also plays an important role in the regulation of cellular commitment of hematopoietic progenitor cells and myeloid cell differentiation.p15can be silenced by several mechanisms, including deletion and hypermethylation of its promoter. Homozygousp15deletion is rare in acute myeloblastic leukemia (AML) and myelodysplastic syndromes (MDS) but frequent in acute lymphoblastic leukemia (ALL). On the contrary, methylation of thep15promoter is identified in some 50% of the patients with AML and MDS, but is less frequent in ALL. The analysis of the 28 studies available in the literature revealed conflicting results (unfavorable, favorable or no impact) that can be due, at least in part, to methodological and/or biological pitfalls. Among those, are the heterogeneity of the methylation patterns of thep15gene and the lack of a comprehensive analysis including transcriptional and translational inactivation that have major impact on its expression. Therefore, detection of thep15mRNA expression (quantitative or not) may represent a more appropriate method to determine the prognostic impact of thep15gene. [ABSTRACT FROM AUTHOR]