TEL gene rearrangement in acute lymphoblastic leukemia: A new genetic marker with prognostic significance

Purpose: TEL gene rearrangements due to the 12;21 chromosomal translocation are the most common molecular genetic abnormality in childhood acute lymphoblastic leukemia (ALL), occurring in approximately 25% of cases with a B-precursor immunophenotype. The limited number of clinically useful genetic markers in this leukemia subtype prompted us to assess TEL status as a predictor of treatment outcome. Patients and Methods: We determined the status of the TEL gene (rearranged or germline) in 188 cases of B-precursor acute leukemia using Southern blot analysis 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 rearranged 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 nonhyperdiploid patients, the odds ratio of an adverse event in the germline TEl group to that for the rearranged TEL group was 4.06 (95% confidence interval, 1.86 to 8.84). The relationship of TEL rearrangement to a favorable prognosis was independent of recognized good-risk features in B- precursor leukemia, including age, initial leukocyte count, and hyperdiploidy. Conclusion: Rearrangement of the TEL gene distinguishes a large subset of children with favorable-prognosis B-precursor leukemia who cannot be identified by standard prognostic features. It may be possible to treat these patients less aggressively without loss of therapeutic efficacy.