Identification of three distinct regions of deletion on the long arm of chromosome 11 in childhood acute lymphoblastic leukemia

Cytogenetic analysis of childhood acute lymphoblastic leukemia (ALL) identi fied deletions of chromosome arm 11q, These observations led us to analyse the loss of heterozygosity (LOH) of chromosome arm 11q in 113 primary child hood ALL samples using 14 microsatellite markers. LOH was found in 18 (16%) patients. Detailed examination identified three distinct regions of deleti on. The first region is flanked by D11S901 and D11S1391 at 11q22-23 contain ing the A TM gene. Mutational analysis suggested that the altered gene in t his region is not the ATM gene. The second region is flanked by D11S614 and D11S924 at 11q23 containing the MLL gene, The third region is flanked by D 11S1356 and D11S614 at 11q23 containing the MLL gene. All the cases with LO H at MLL locus lacked detectable MLL gene rearrangements. In addition, 20 c hildren have been studied both at initial diagnosis and relapse; none of th e individuals who relapsed acquired LOH of 11q, suggesting that 11q deletio ns were infrequently involved in the progression of childhood ALL. Children with 11q LOH had a good response to induction chemotherapy (P=0.015), Thes e data suggest that alterations of putative tumor suppressor genes on 11q a re important events in development of childhood ALL. Our map provides impor tant information toward cloning putative tumor suppressor genes associated with childhood ALL.