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Scientific article
English

Polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia

Published inPharmacogenomics journal, vol. 12, no. 5, p. 386-394
Publication date2012
Abstract

Multidrug resistance-related proteins (MRPs) 2, 3 and 5 are involved in the efflux of drugs used in acute lymphoblastic leukemia (ALL) treatment. Polymorphisms of these genes were investigated for an association with treatment responses in 273 childhood ALL patients. The MRP3 A-189 allele of the regulatory AT polymorphism was associated with reduced event-free survival (P=0.01). The results remained significant after adjustment for multiple comparisons and in the multivariate analysis. Among patients with an event, the A-189 carriers had significantly higher methotrexate plasma levels (P=0.03). MRP3 A-189 also conferred four times higher risk of a relapse in central nervous system (P=0.01). Patients with this allele tended to have lower frequency of thrombocytopenia grade 2 (P=0.06). Gene reporter assay showed that the haplotype tagged by the A-189 had higher promoter activity (P≤0.01). In conclusion, MRP3 A-189 T polymorphism was associated with treatment responses in ALL, likely due to the change in MRP3 efflux.

Keywords
  • Alleles
  • Biomarkers, Pharmacological
  • Disease-Free Survival
  • Genetic Association Studies
  • Genotype
  • Haplotypes
  • Humans
  • Methotrexate/therapeutic use
  • Multidrug Resistance-Associated Proteins/genetics/metabolism
  • Polymorphism, Single Nucleotide/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy/genetics
  • Treatment Outcome
Citation (ISO format)
ANSARI DJABERI, Marc Georges et al. Polymorphism in multidrug resistance-associated protein gene 3 is associated with outcomes in childhood acute lymphoblastic leukemia. In: Pharmacogenomics journal, 2012, vol. 12, n° 5, p. 386–394. doi: 10.1038/tpj.2011.17
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Article (Published version)
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ISSN of the journal1470-269X
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