FREQUENT CLONAL LOSS OF HETEROZYGOSITY (LOH) IN THE CHROMOSOMAL REGION 1P32 OCCURS IN CHILDHOOD T-CELL ACUTE LYMPHOBLASTIC-LEUKEMIA (T-ALL)CARRYING REARRANGEMENTS OF THE TAL1 GENE

Deletions and chromosomal translocations involving the 1p32 region, ar e frequently observed in T cell acute lymphoblastic leukemia (T-ALL). One of the most common genetic changes is the breakage of the TAL1 gen e, which was originally described to be involved in the T-ALL carrying the t(1;14)(p32;q11) translocation. Site specific deletions in the TA LI gene are reported to occur in 12-26% of T-ALL with apparently norma l karyotype. In order to investigate the presence of other subkaryotyp ic abnormalities involving the 1p32 chromosomal region, where TAL1 gen e is mapped, we assessed losses of heterozygosity (LOH) for microsatel lite markers, in a series of 22 children with T-ALL. Microsatellite po lymorphic markers flanking the TAL1 gene (D1S211, D1S197, D1S200 and D 1S220) were analyzed to detect LOH. Eight patients displayed LOH for a t least one of the markers, suggesting the existence of hot spot regio ns at the short arm of chromosome 1. Two out of 11 with no molecular e vidences of TAL1 gene involvement, compared to six out of 11 in the gr oup of TAL1 rearranged gene, showed LOH at 1p32. TAL1 gene rearrangeme nts and clonal LOH may represent two independent events, but could be related to the same causes. For the first time this study provides evi dences that LOH at 1p32 region, occurs in T-ALL in the same region kno wn to be involved in chromosomal deletions and translocations. LOH map ping may help to define the location of a new putative tumor-suppresso r gene implicated in the trasformation and progression of children T-A LL.