TEL GENE REARRANGEMENT IN ACUTE LYMPHOBLASTIC-LEUKEMIA - A NEW GENETIC-MARKER WITH PROGNOSTIC-SIGNIFICANCE

Purpose: TEL gene rearrangements due to the 12;21 chromosomal transloc ation are the most common molecular genetic abnormality in childhood a cute lymphoblastic leukemia (ALL), occurring in approximately 25% of c ases with a B-precursor immunophenotype. The limited number of clinica lly useful genetic markers in this leukemia subtype prompted vs to ass ess TEL status as a predictor of treatment outcome. Patients and Metho ds: We determined the status of the TEL gene (rearranged or germline) in 188 cases of B-precursor acute leukemia using Southern blot analysi s and related the findings to event-free survival. All comparisons of outcome were stratified by treatment regimen, risk classification, age , and leukocyte count. Results: Forty-eight patients (26%) had a rearr anged TEL gene, At 5 years of follow-up, an estimated 91% +/- 5% (SE) of this group were event-free survivors, compared with only 65% +/- 5% of the group with germline TEL (stratified log-rank P = .011), For no nhyperdiploid patients, the odds ratio of an adverse event in the germ line TEL group to that for the rearranged TEL group was 4.06 (95% conf idence interval, 1.86 to 8.84), The relationship of TEL rearrangement to a favorable prognosis was independent of recognised good-risk featu res in B-precursor leukemia, including age, initial leukocyte count,an d hyperdiploidy. Conclusion: Rearrangement of the TEL gene distinguish es a large subset of children with favorable-prognosis B-precursor leu kemia who cannot be identified by standard prognostic features. It may be possible to treat these patients less aggressively without loss of therapeutic efficacy. (C) 1997 by American Society of Clinical Oncolo gy.