TY - JOUR T1 - TNF-α SNP rs1800629 and risk of relapse in childhood acute lymphoblastic leukemia: relation to immunophenotype. JF - Pharmacogenomics Y1 - 2014 A1 - Franca, Raffaella A1 - Rebora, Paola A1 - Athanasakis, Emmanouil A1 - Favretto, Diego A1 - Verzegnassi, Federico A1 - Basso, Giuseppe A1 - Tommasini, Alberto A1 - Valsecchi, Maria Grazia A1 - Decorti, Giuliana A1 - Rabusin, Marco KW - Adolescent KW - Antineoplastic Agents KW - Child KW - Child, Preschool KW - Drug Resistance, Neoplasm KW - Female KW - Genotype KW - Humans KW - Infant KW - Leukemia, Lymphocytic, Chronic, B-Cell KW - Male KW - Phenotype KW - Precursor Cell Lymphoblastic Leukemia-Lymphoma KW - Precursor T-Cell Lymphoblastic Leukemia-Lymphoma KW - Recurrence KW - Risk Assessment KW - Steroids KW - Tumor Necrosis Factor-alpha AB -

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.

VL - 15 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24798719?dopt=Abstract ER -