Homozygous Deletion of the p16 Gene in Childhood Acute Lymphoblastic Leukemia

pl6/MTSl (multiple tumor suppressor)/CDK4I (cyclin-dependent kinase 4 inhibitor) is a putative tumor suppressor gene involved in carcinogenesis in a wide variety of tissues. To study the involvement of the pl6 gene in leukemogenesis, we performed Southern blot analyses in chilhood acute lymphoblastic leukemia (ALL) DNA sample from 110 children with primary ALL (22 T-ALL, 88 precursor-B ALL) revealed homozygous deletions in 29/110 cases (26%), and showed a significant association with the T-lineage [17/22 T-ALL (77%) versus 12/88 precursor-B ALL (14%); 0.001]. Additionally, hemizygous deletions were observed in 2 cases of T-ALL and 9 of precursor-B ALL. None of 19 cases with pl6 deletions showed evidence of germline alterations. This study demonstrates that homozygous loss of the pl6 gene represents the most frequent genetic alteration in childhood ALL, and suggests that inactivation of pl6 is a critical event in leukemogenesis.