The OPN gene polymorphism confers the susceptibility and response to Ara-C based chemotherapy in Chinese AML patients

Cell Physiol Biochem. 2015;35(1):175-83. doi: 10.1159/000369685. Epub 2015 Jan 2.

Abstract

Aim: To investigate the possible association between the Osteopontin (OPN) gene polymorphisms and the susceptibility and chemotherapy response of acute myeloid leukemia patients.

Methods: A total of 381 patients with de nova AML and 430 healthy controls were enrolled. All patients received Ara-C-based standard induction chemotherapy regimens, and the treatment response was evaluated. Several polymorphisms in the human OPN encoding gene have been identified. The OPN) gene polymorphisms at 3 loci, namely, -156 GG>G, -443 C>T and -66T>G were determined.

Results: We identified that the -443C>T polymorphism was the only one which is closely related to AML. Compared with the -443TT carriers, our data showed that the -443CC genotype carriers were significantly related to a higher risk for AML. The -443CC genotype was also more prevalent in poor response groups than in good response group. The -443CC carriers are more likely to have poor response to AML treatment. Cellular assay indicated that the leukemic cell lines receiving the OPN -443C transfection have a significantly lower apoptosis rate to Ara-C treatment compared to cell lines transfected with -443T.

Conclusion: The findings of this study suggest OPN-443C>T gene polymorphism may be sued as a molecular for susceptibility and chemotherapy response of AML.

MeSH terms

  • Adult
  • Alleles
  • Antimetabolites, Antineoplastic / therapeutic use
  • Apoptosis
  • Cell Line, Tumor
  • China
  • Cytarabine / therapeutic use
  • Disease Susceptibility
  • Female
  • Genotype
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Middle Aged
  • Osteopontin / blood
  • Osteopontin / genetics*
  • Osteopontin / metabolism
  • Polymorphism, Single Nucleotide*
  • Transfection

Substances

  • Antimetabolites, Antineoplastic
  • Cytarabine
  • Osteopontin