INVOLVEMENT OF CDKN2 (P16(INK4A) MTS1) AND P15(INK4B)/MTS2 IN HUMAN LEUKEMIAS AND LYMPHOMAS/

CDKN2 (p(16INK4A)/MTS1) and p(15INK4B)/MTS2 have been shown recently t o be potent inhibitors of the cyclin D/cyclin-dependent kinase 4 compl er. Both genes are candidates for the putative tumor suppressor gene l ocated at chromosome 9p21. We examined a series of 14 hematopoietic ce ll lines and 117 primary lymphoid tumors for deletion and mutation of these genes. The primary tumors included 65 T-cell malignancies and 52 B-cell malignancies. The cell line study revealed 4 of 4 T-ALL lines to have homozygous deletions of CDKN2. Two of the 4 lines also show ed homozygous deletions of MTS2, while the remaining 2 lines retained bo th MTS2 alleles. In the primary tumors, homozygous deletions of both C DKN2 and MTS2 were found in 35% of the T-ALL/lymphoblastic lymphoma (8 of 23), Homozygous deletions of both genes also occurred in 1 of 3 pr ecursor B-ALLs. PCR-single strand conformational polymorphism analysis of CDKN2 exons 2 and 3 and MTS2 exon 2 failed to demonstrate mutation s in either CDKN2 or MTS2 in any of the T- or B-cell malignancies, wit h two possible exceptions. These results are consistent with a role fo r CDKN2 and/or MTS2 in the pathogenesis of some IS mphoid leukemia/lym phomas, particularly in T-ALL/lymphoblastic lymphoma.