TNF-α SNP rs1800629 and Risk of Relapse in Childhood Acute Lymphoblastic Leukemia: Relation to Immunophenotype

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 submitted 12 September 2013; Revision submitted 16 December 2013

KEYWORDS::

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

Financial & competing interests disclosure

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf(available on request from the corresponding author) and declare: no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. Supporting foundations: Italian Ministry of Health, Fondazione Benefica Alberto e Kathleen Casali. R Franca and D Favretto are recipient fellowships from IRCCS Burlo Garofolo, Trieste. Grant from the European Commission (FP7-HEALTH-F2–2011 261474) to P Rebora and MG Valsecchi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf(available on request from the corresponding author) and declare: no support from any organization for the submitted work, no financial relationships with any organizations that might have an interest in the submitted work in the previous 3 years and no other relationships or activities that could appear to have influenced the submitted work. Supporting foundations: Italian Ministry of Health, Fondazione Benefica Alberto e Kathleen Casali. R Franca and D Favretto are recipient fellowships from IRCCS Burlo Garofolo, Trieste. Grant from the European Commission (FP7-HEALTH-F2–2011 261474) to P Rebora and MG Valsecchi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.