12P ABNORMALITIES AND THE TEL GENE (ETV6) IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Although abnormalities involving the short arm of chromosome 12 (12p) are one of the most frequently observed rearrangements in childhood, a cute lymphoblastic leukemia (ALL), little is known about the frequency of different structural abnormalities and their relationship to the s tatus of the ETV6 (also named TEL) gene in this region, Of 815 childre n with newly diagnosed ALL, 94 (11.5%) had a total of 104 cytogenetic 12p abnormalities. Loss of genetic material was observed in 67 (64%) o f these abnormalities. Cases with 12p alterations had a much lower fre quency of hyperdiploidy greater than 50 (7%) than did the ALL populati on in general, but these cases had a similar distribution of immunophe notype and similar 5-year event-free survival (70% +/- 5% SE v 64% +/- 2%, P = .64). Rearrangement of the ETV6 gene was identified in 36 (56 %) of 64 cases evaluated, The ETV6-CBFA2 (TEL-AML1) fusion transcript was found in 25 (66%) of 38 cases evaluated, and all but one of these showed ETV6 rearrangement. Importantly, ETV6 rearrangement was associa ted with a favorable prognosis (5-year event-free survival: 89% +/- 6% v 60% +/- 1%, P < .01). We conclude that most but not all 12p cytogen etic abnormalities in childhood ALL involve ETV6, and that rearrangeme nt of ETV6 is associated with a favorable treatment outcome. (C) 1997 by The American Society of Hematology.