TNF-α SNP rs1800629 and risk of relapse in childhood acute lymphoblastic leukemia: relation to immunophenotype

Pharmacogenomics. 2014 Apr;15(5):619-27. doi: 10.2217/pgs.13.249.

Abstract

Aim: In the AIEOP-BFM ALL (Associazione Italiana Ematologia Oncologia Pediatrica-Berlin Frankfurt Münster acute lymphoblastic leukemia) 2000 protocol, 70% of relapsed patients had favorable prognostic features and fell within less intensive polychemotherapeutic regimens, suggesting the need for better assessing lower risk stratification.

Materials & methods: A novel two-phase study design selected 614 children to be genotyped for TNF-α SNP rs1800629 (-308G>A). A weighted Cox model was applied to evaluate the SNP effect on hazard of relapse, adjusting for immunophenotype, risk group, age and gender and including interaction terms.

Results: Significant interaction was found with immunophenotypes (p = 0.0007, with minor allele genotypes being adverse genetic markers in B-cell acute lymphoblastic leukemia and protective ones in T-cell acute lymphoblastic leukemia), and also with risk protocols (p = 0.0041, with minor allele genotypes as prognostic factor of relapse for standard risk patients [only one T-cell acute lymphoblastic leukemia in the subgroup analyzed]).

Conclusion: The presence of at least one A allele in TNF-α SNP rs1800629 should suggest a closer monitoring in B-cell acute lymphoblastic leukemia standard risk patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Agents / therapeutic use
  • Child
  • Child, Preschool
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Genotype
  • Humans
  • Infant
  • Leukemia, Lymphocytic, Chronic, B-Cell / genetics
  • Male
  • Phenotype
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Recurrence
  • Risk Assessment
  • Steroids / therapeutic use
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • Antineoplastic Agents
  • Steroids
  • Tumor Necrosis Factor-alpha