Mohammad Salem Hareedy1,2, Ehab S El Desoky1, Jean-Baptiste Woillard2,3,4, Romany Helmy Thabet1, Amany Mohamad Ali5, Pierre Marquet2,3,4, Nicolas Picard2,3,5. 1. Department of Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt. 2. Inserm, UMR-850, Limoges, France. 3. Department of Pharmacology, Toxicology & Pharmacovigilance, CHU Limoges, Limoges, France. 4. Faculty of Medicine, Laboratory of Medical Pharmacology, University of Limoges, Limoges, France. 5. South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Abstract
AIM: We investigated the associations between variants in genes coding for enzymes and transporters related to the 6-mercaptopurine pathway and clinical outcomes in pediatric patients with acute lymphoblastic leukemia. MATERIALS & METHODS: Statistical association between gender, age and genotypes of selected SNPs, and the risks of hematological toxicity and relapse were investigated using a Cox proportional hazard model in 70 acute lymphoblastic leukemia patients from upper Egypt. RESULTS: We found significant associations between ITPA, IMPDH1, SLC29A1, SLC28A2, SLC28A3 and ABCC4 SNPs and one or more of the hematological toxicity manifestations (neutropenia, agranulocytosis and leukopenia); age was significantly related to relapse. CONCLUSION: Genetic polymorphisms in enzymes and transporters involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.
AIM: We investigated the associations between variants in genes coding for enzymes and transporters related to the 6-mercaptopurine pathway and clinical outcomes in pediatric patients with acute lymphoblastic leukemia. MATERIALS & METHODS: Statistical association between gender, age and genotypes of selected SNPs, and the risks of hematological toxicity and relapse were investigated using a Cox proportional hazard model in 70 acute lymphoblastic leukemiapatients from upper Egypt. RESULTS: We found significant associations between ITPA, IMPDH1, SLC29A1, SLC28A2, SLC28A3 and ABCC4 SNPs and one or more of the hematological toxicity manifestations (neutropenia, agranulocytosis and leukopenia); age was significantly related to relapse. CONCLUSION: Genetic polymorphisms in enzymes and transporters involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.
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