HIGH-FREQUENCY OF HOMOZYGOUS DELETIONS OF CDK4I GENE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

To determine the incidence of homozygous deletions of the newly identi fied tumour suppressor gene, CDK4I, molecular genomic DNA analyses by PCR technique were performed on primary neoplastic cells from 22 child hood acute leukaemias obtained at presentation. The blast cells derive d in all the analysed cases from bone marrow, We found that none of ac ute myeloblastic leukaemias (four cases) showed the CDK4I alteration, whereas 6/13 (46%) common acute lymphoblastic leukaemias (ALLs) displa yed homozygous deletions. Moreover, and even more important, all the b lasts purified from ALLs derived from early lymphoid precursors (three early-T ALLs and two pre-B ALLs) showed the absence of CDK4I gene, Wh en the entire coding sequence of the CDK4I gene from samples without h omozygous deletions was analysed by the single-strand conformational p olymorphism method, no point mutations were identified. These results demonstrate that CDK4I gene deletions are very frequent and probably e arly events in childhood acute leukaemias of lymphoid origin and espec ially in early-T and pre-B ALLs. Moreover, the molecular mechanism of the loss of function of the gene is correlated, at least in childhood ALLs, almost exclusively to deletions and not to point mutations.