DIFFERENT PATTERNS OF HOMOZYGOUS P-16(INK4A) AND P15(INK4B) DELETIONSIN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIAS CONTAINING DISTINCT E2A TRANSLOCATIONS

The p16(INK4A)(p16) and p15(INK4B) (p15) tumor suppressor genes are in activated by homozygous gene deletion and p15 promoter hypermethylatio n in a significant proportion of childhood acute lymphoblastic leukemi as (ALLs). However, little is known about the potential association be tween p16/p15 gene alterations and specific genetic abnormalities impl icated in leukemogenesis. The t(1;19)(q23;p13) and t(17;19)(q21-22;p13 ) are non-random translocations observed in childhood ALL that create distinct E2A fusion proteins: E2A-PBX1 and E2A-HLF, respectively. Prev iously, a negative assocation was found between the t(1;19) and homozy gous p16/p15 deletions. In this study we determined p16 and p15 gene s tatus in additional t(1;19)(+) ALLs and compared this incidence to tha t observed in t(17;19)(+) ALLs. No homozygous p16 or p15 deletions wer e observed among 13 t(1;19)(+) ALLs analyzed. In contrast, homozygous deletions of both p16 and p15 were present in two of four 1(17;19)(+) ALLs. None of 10 t(1;19)(+) ALLs contained p15 promoter hypermethylati on. In contrast, one of the two t(17;19)(+) ALLs that lacked p15/p16 h omozygous deletions showed probable hemizygous p15 hypermethylation. W e conclude that homozygous p16 and/or p15 deletions and p15 hypermethy lation rarely accompany E2A-PBX1 fusion, but occur in concert with E2A -HLF fusion in a subset of t(17;19)(+) ALLs. These findings suggest th at there may be different modes of cooperative leukemogenesis in ALLs associated with different E2A fusion proteins.