Francesco Ceppi1, Vincent Gagné2, Laurance Douyon2, Camille J Quintin2, Antonella Colombini3, Rosanna Parasole4, Barbara Buldini5, Giuseppe Basso5, Valentino Conter3, Giovanni Cazzaniga6, Maja Krajinovic2,7,8. 1. Pediatric Hematology-Oncology Unit & Pediatric Hematology-Oncology Research Laboratory, Division of Pediatrics, Department of Woman-Mother-Child, University Hospital of Lausanne, 1004 Lausanne, Switzerland. 2. Charles-Bruneau Cancer Center, CHU Sainte-Justine Research Center, Montreal, QC, H3T1C5, Canada. 3. Department of Pediatrics, University of Milano-Bicocca, Ospedale S Gerardo, 20835 Monza, Italy. 4. Department of Pediatric Hemato-Oncology, Santobono-Pausilipon Hospital, 80129 Naples, Italy. 5. Department of Woman & Child Health, Laboratory of Haematology-Oncology, University of Padova, 35128 Padova, Italy. 6. Centro Ricerca Tettamanti, Department of Pediatrics, University Milano Bicocca, 20835 Monza, Italy. 7. Department of Pediatrics, Faculty of Medicine, University of Montreal, Montreal, QC, H4A 3J1, Canada. 8. Department of Pharmacology & Physiology, Faculty of Medicine, University of Montreal, Montreal, QC, H3C 3J7, Canada.
Abstract
AIM: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. METHODS: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. RESULTS: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). CONCLUSION: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.
AIM: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses. METHODS: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome. RESULTS: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%). CONCLUSION: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment.
Authors: Nicolas Waespe; Sven Strebel; Tiago Nava; Chakradhara Rao S Uppugunduri; Denis Marino; Veneranda Mattiello; Maria Otth; Fabienne Gumy-Pause; André O Von Bueren; Frederic Baleydier; Luzius Mader; Adrian Spoerri; Claudia E Kuehni; Marc Ansari Journal: BMJ Open Date: 2022-01-24 Impact factor: 2.692
Authors: Hui Zhang; Anthony Pak-Yin Liu; Meenakshi Devidas; Shawn Hr Lee; Xueyuan Cao; Deqing Pei; Michael Borowitz; Brent Wood; Julie M Gastier-Foster; Yunfeng Dai; Elizabeth Raetz; Eric Larsen; Naomi Winick; W Paul Bowman; Seth Karol; Wenjian Yang; Paul L Martin; William L Carroll; Ching-Hon Pui; Charles G Mullighan; William E Evans; Cheng Cheng; Stephen P Hunger; Mary V Relling; Mignon L Loh; Jun J Yang Journal: J Natl Cancer Inst Date: 2021-04-06 Impact factor: 11.816