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Pharmacogenomics. 2015;16(10):1119-34. doi: 10.2217/PGS.15.62. Epub 2015 Aug 3.

Genetic variants in 6-mercaptopurine pathway as potential factors of hematological toxicity in acute lymphoblastic leukemia patients.

Author information

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.

KEYWORDS:

6-mercaptopurine; childhood acute lymphoblastic leukemia; leukopenia; neutropenia; pharmacogenetics; relapse

PMID:
26237184
DOI:
10.2217/PGS.15.62
[Indexed for MEDLINE]

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