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

Raffaella Franca, Paola Rebora, Emmanouil Athanasakis, Diego Favretto, Federico Verzegnassi, Giuseppe Basso, Alberto Tommasini, Maria Grazia Valsecchi, Giuliana Decorti, Marco Rabusin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)619-627
Number of pages9
JournalPharmacogenomics
Volume15
Issue number5
DOIs
Publication statusPublished - 2014

Keywords

  • pediatric acute lymphoblastic leukemia
  • prognostic genetic factors
  • relapse
  • risk-adapted polychemotherapy
  • TNF-α rs1800629 (-308G>A)

ASJC Scopus subject areas

  • Pharmacology
  • Genetics
  • Molecular Medicine
  • Medicine(all)

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