Role of the cyclin-dependent kinase 4 and 6 inhibitor gene family p15, p16, p18 and p19 in leukemia and lymphoma.

Neoplastic diseases are proliferative disorders characterized by uncoordinated cell growth. Cellular proliferation follows an orderly progression through the cell cycle, which is governed by different cyclins and cyclin dependent kinases (CDKs). Recently, CDK-inhibitors, which are a new class of small proteins involved in the negative regulation of the cell cycle, have been identified by virtue of their ability to interact physically with cyclin/CDK-complexes. As the genes encoding the CDK4- and CDK6-inhibitors (CDK4/6-inhibitors) p16INK4A/CDKN2/MTS1 and p15INK4B/MTS2 have been found to be altered in many cancer cell lines and primary neoplastic tissues, CDK-inhibitors in general and CDK4/6-inhibitors in particular are now a se: of candidate tumor suppressors. The p15 and p16 genes map to a region frequently deleted in lymphoid neoplasms. Therefore, considerable efforts have been made to determine the role of CDK4/6-inhibitors in hematologic malignancies: This article will review alterations of components of the cell-cycle machinery in brief and summarize the role of the CDK4/6-inhibitors p16INK4A, p15INK4B, p18INK4C and p19INK4D in leukemias and lymphomas.