MOLECULAR ANALYSIS OF CYCLIN-DEPENDENT KINASE INHIBITORS IN HUMAN LEUKEMIAS

Recurrent anomalies of the short arm of chromosome 9, including inters titial deletions and translocations, have often been described. Recent ly two cyclin-dependent kinase inhibitors, known as P16(INK4A/MTS1) an d P15(INK4B/MTS2), which map to 9p21, have been found deleted in a wid e range of tumors and particularly in leukemic cells. We report here S outhern blot analyses of cyclin-dependent kinase inhibitors (P16, P15, P21, and P27) status in primary tumoral cells of 121 patients with ac ute lymphoblastic leukemias, 85 patients with acute myeloid leukemias and 42 patients with B-chronic lymphocytic leukemias. P16 inactivation was found in 25 of 38 T-ALLs and in 28 of 83 B-lineage ALLs. In eight cases (three T-ALLs and five B-lineage ALLs), one or both alleles of P16 locus were rearranged. In these cases, breakpoints occurred within the two major breakpoints cluster regions previously described In T-A LLs. Homozygous P16 deletions were observed in two of 85 AMLs but in n one of the 42 B-CLL cases tested. Our results suggest that P16 inactiv ation are the most frequent event observed in ALL (44%), are quite rar e in AML (<2%) and seem to be absent in CLL. Search for P27 and P21 de letion was negative in B/T-lineage ALLs and monoallelic deletions of P 27 were found in four AML cases (5%).