Cylin/CDK inhibitors of the 9p21 chromosomal region and hematological malignancies
9p21 chromosomal region contains p15INK4b and p16INK4a genes which regulate G1 phase of the cell cycle by inhibition of cyclin-cyclin dependent kinases. The p19ARF protein is translated from an alternative transcript of the p16INK4a gene and regulates G1 and G2 phase of the cell cycle by degradation of the MDM2 protein. p16INK4a and p15INK4b gene homozygous deletions occur mostly in acute lymphoblastic leukemia, ATL secondary to HTLV1 infection, and some lymphoma. Point mutations of p16INK4a or p15INK4b gene seem to be extremely rare, however selective methylations of the p15INK4b or p16INK4a promoters are frequently found in myelodysplastic syndromes and acute leukemias, or lymphomas and myelomas respectively. These data demonstrate that inactivation of gene of the 9p21 region is currently the main molecular event found in hematological malignancies.
B
Quesnel