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.
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.
Authors: D Bhojwani; D Pei; J T Sandlund; S Jeha; R C Ribeiro; J E Rubnitz; S C Raimondi; S Shurtleff; M Onciu; C Cheng; E Coustan-Smith; W P Bowman; S C Howard; M L Metzger; H Inaba; W Leung; W E Evans; D Campana; M V Relling; C-H Pui Journal: Leukemia Date: 2011-08-26 Impact factor: 11.528
Authors: S Knuutila; Y Aalto; K Autio; A M Björkqvist; W El-Rifai; S Hemmer; T Huhta; E Kettunen; S Kiuru-Kuhlefelt; M L Larramendy; T Lushnikova; O Monni; H Pere; J Tapper; M Tarkkanen; A Varis; V M Wasenius; M Wolf; Y Zhu Journal: Am J Pathol Date: 1999-09 Impact factor: 4.307
Authors: Michael J Borowitz; Meenakshi Devidas; Stephen P Hunger; W Paul Bowman; Andrew J Carroll; William L Carroll; Stephen Linda; Paul L Martin; D Jeanette Pullen; David Viswanatha; Cheryl L Willman; Naomi Winick; Bruce M Camitta Journal: Blood Date: 2008-04-03 Impact factor: 22.113
Authors: Jeffrey E Rubnitz; David Wichlan; Meenakshi Devidas; Jonathan Shuster; Stephen B Linda; Joanne Kurtzberg; Beverly Bell; Stephen P Hunger; Allen Chauvenet; Ching-Hon Pui; Bruce Camitta; Jeanette Pullen Journal: J Clin Oncol Date: 2008-05-01 Impact factor: 44.544
Authors: Allen R Chauvenet; Paul L Martin; Meenakshi Devidas; Stephen B Linda; Beverly A Bell; Joanne Kurtzberg; Jeanette Pullen; Mark J Pettenati; Andrew J Carroll; Jonathan J Shuster; Bruce Camitta Journal: Blood Date: 2007-04-18 Impact factor: 22.113