AIM: In the AIEOP-BFM 2000 trial, 15% of pediatric patients treated according to risk-adapted polychemotherapeutic regimens relapsed. The present study aimed to investigate the influence of GST-M1 and GST-T1 deletions on clinical outcome of children with acute lymphoblastic leukemia treated according to the AIEOP-BFM ALL 2000 study protocol. MATERIALS & METHODS: A novel-design, two-phase study was applied to select a subsample of 614 children to be genotyped for the deletions of GST genes. Cumulative incidence of relapse was then estimated by weighted Kaplan-Meier analysis, and the Cox model was applied to evaluate the effect of GST-M1 and GST-T1 isoenzyme deletions on relapse. RESULTS: No overall effect was found, but the GST-M1 deletion was associated with better clinical outcome within prednisone poor-responder patients (hazard ratio [HR]: 0.45; 95% CI: 0.23-0.91; p = 0.026), whereas the GST-T1 deletion was associated with worse outcome in the standard-risk group (HR: 4.62; 95% CI: 1.04-20.6; p = 0.045) and within prednisone good responders (HR: 1.62; 95% CI: 1.02-2.58; p = 0.041). CONCLUSION: Our results show that GST-M1 and GST-T1 homozygous deletions have opposite correlation with relapse, the former being protective and the latter unfavourable in specific subsets of acute lymphoblastic leukemia patients.
AIM: In the AIEOP-BFM 2000 trial, 15% of pediatric patients treated according to risk-adapted polychemotherapeutic regimens relapsed. The present study aimed to investigate the influence of GST-M1 and GST-T1 deletions on clinical outcome of children with acute lymphoblastic leukemia treated according to the AIEOP-BFM ALL 2000 study protocol. MATERIALS & METHODS: A novel-design, two-phase study was applied to select a subsample of 614 children to be genotyped for the deletions of GST genes. Cumulative incidence of relapse was then estimated by weighted Kaplan-Meier analysis, and the Cox model was applied to evaluate the effect of GST-M1 and GST-T1 isoenzyme deletions on relapse. RESULTS: No overall effect was found, but the GST-M1 deletion was associated with better clinical outcome within prednisone poor-responder patients (hazard ratio [HR]: 0.45; 95% CI: 0.23-0.91; p = 0.026), whereas the GST-T1 deletion was associated with worse outcome in the standard-risk group (HR: 4.62; 95% CI: 1.04-20.6; p = 0.045) and within prednisone good responders (HR: 1.62; 95% CI: 1.02-2.58; p = 0.041). CONCLUSION: Our results show that GST-M1 and GST-T1 homozygous deletions have opposite correlation with relapse, the former being protective and the latter unfavourable in specific subsets of acute lymphoblastic leukemiapatients.
Authors: R Franca; P Rebora; N Bertorello; F Fagioli; V Conter; A Biondi; A Colombini; C Micalizzi; M Zecca; R Parasole; F Petruzziello; G Basso; M C Putti; F Locatelli; P d'Adamo; M G Valsecchi; G Decorti; M Rabusin Journal: Pharmacogenomics J Date: 2015-12-08 Impact factor: 3.550
Authors: Simona Jurkovic Mlakar; Satyanarayana Chakradhara Rao Uppugunduri; Tiago Nava; Vid Mlakar; Hadrien Golay; Shannon Robin; Nicolas Waespe; Mohamed Aziz Rezgui; Yves Chalandon; Jaap Jan Boelens; Robert G M Bredius; Jean-Hugues Dalle; Christina Peters; Selim Corbacioglu; Henrique Bittencourt; Maja Krajinovic; Marc Ansari Journal: J Cancer Res Clin Oncol Date: 2021-09-09 Impact factor: 4.553