p16^ink4a Gene and Hematological Malignancies

Abstract

Progression of eukaryotic cells through major cell cycle transitions is mediated by sequential assembly and activation of regulators, the cyclin-dependent CDKkinases (CDKs). Recent studies have identified different CDK inhibítory genes (CDKis), and two of them, p16^ink4a/MTS1/CDKN2 and p15^ink4b/MTS2 are both mapped to chromosome 9p21 and inhibit cyclin D-CDK4 and -CDK6 complexes. A feedback regulatory loop involving pRb, p 16^ink4a, and CDKs seems to regulate G1/S phases transition. p16^ink4a and p15^ink4b are deleted in high frequency in human cell lines and in some fresh solid tumors. Point mutations of p16^ink4a have also been sequenced, especially in familial melanomas and digestive cancers but preferential mechanism of p16^ink4a/p15^ink4b inactivation seems to be bial-lelic deletion. In hematological malignancies, homozygous deletions of p16^ink4a and p15^ink4b occur frequently in acute lymphoblastic leukemia (ALL) (14—40%), lymphoid type blast crisis of chronic myeloid leukemia (CML), and adult T cell leukemia (ATL), but p16^ink4a deletions are more frequent than p15^ink4b deletions, and hemizygous deletions of either p16^ink4a and p15^ink4b are rare. In ALL an association of homozygous deletions of p16^ink4a and p15^ink4b, and T-lineage, 9p abnormalities, and prognostic factors was found in some but not all reports. This review presents recent data on p16^ink4a and p15^ink4b functions and analyses their implications in hematological malignancies.

Key Words:

• p16ink 4a gene
• hematological malignancy