THE 12-21-TRANSLOCATION INVOLVING TEL AND DELETION OF THE OTHER TEL ALLELE - 2 FREQUENTLY ASSOCIATED ALTERATIONS FOUND IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

A recurrent t(12;21)(p13;q22) has recently been described in human acu te lymphoblastic leukemias (ALLs). This translocation fuses TEL and AM L1, two genes previously cloned from translocation breakpoints in myel oid leukemias. In addition, allelic loss of the TEL gene can be detect ed in 15% to 22% of childhood ALLs. In the present study, we have soug ht allelic deletions of TEL and the presence of the t(12;21) in 50 chi ldren with B-lineage ALL, using a combination of microsatellite typing , fluorescent in situ hybridization (FISH), and analysis of the fusion transcripts resulting from the TEL-AML1 gene fusion. Our results indi cate that the association between the t(12;21) and the deletion of the nontranslocated allele of TEL is among the most frequent abnormalitie s observed in B-lineage ALLs. FISH analysis using several cosmid probe s showed that, in one patient with a t(12;21) translocation involving TEL, the second allele had an intragenic deletion. This observation po ints to TEL as the actual target of 12p12-13 deletions in patients tha t associate a t(12;21) with a deletion. The TEL-AML1 fusion RNA was fo und in all patients with the t(12;21) whereas the reciprocal AML1-TEL transcript was only found in a subset of patients, suggesting that onl y the protein product encoded by TEL-AML1 is likely to play a role in leukemogenesis. The observation that, in two patients with the t(12;21 ), a deletion of TEL was only present in a subclone indicates that thi s deletion was a secondary event that occurred after the translocation . The frequent occurrence of TEL deletions in patients with t(12;21) s uggests that the deletion of the normal TEL allele subsequent to the t (12;21) provides a further proliferative advantage to leukemic cells. (C) 1996 by The American Society of Hematology.