title: Genetic variants in 6-mercaptopurine pathway as potential factors of hematological toxicity in acute lymphoblastic leukemia patients.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Genetic polymorphisms in enzymes and transporters involved in the 6-mercaptopurine pathway should be considered during its use to avoid hematological toxicity.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt.|Inserm, UMR-850, Limoges, France.
authors.forename: Mohammad Salem
authors.initials: MS
authors.lastname: Hareedy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt.
authors.forename: Ehab S
authors.initials: ES
authors.lastname: El Desoky
authors.affiliation: Inserm, UMR-850, Limoges, France.|Department of Pharmacology, Toxicology & Pharmacovigilance, CHU Limoges, Limoges, France.|Faculty of Medicine, Laboratory of Medical Pharmacology, University of Limoges, Limoges, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Woillard
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt.
authors.forename: Romany Helmy
authors.initials: RH
authors.lastname: Thabet
authors.affiliation: South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
authors.forename: Amany Mohamad
authors.initials: AM
authors.lastname: Ali
authors.affiliation: Inserm, UMR-850, Limoges, France.|Department of Pharmacology, Toxicology & Pharmacovigilance, CHU Limoges, Limoges, France.|Faculty of Medicine, Laboratory of Medical Pharmacology, University of Limoges, Limoges, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.affiliation: Inserm, UMR-850, Limoges, France.|Department of Pharmacology, Toxicology & Pharmacovigilance, CHU Limoges, Limoges, France.|South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Picard
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004534:Egypt; D005260:Female; D005838:Genotype; D006402:Hematologic Diseases / Q000139:chemically induced* / Q000235:genetics; D006801:Humans; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects* / Q000627:therapeutic use*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D015122:Mercaptopurine
keywords: 6-mercaptopurine; childhood acute lymphoblastic leukemia; leukopenia; neutropenia; pharmacogenetics; relapse