FAS promoter polymorphism: Outcome of childhood acute myeloid leukemia. A children's oncology group report

Parinda A. Mehta, Robert B. Gerbing, Todd A. Alonzo, James S. Elliott, Tiffanya Zamzow, Michelle Combs, Emily Stover, Julie A. Ross, John P. Perentesis, Soheil Meschinchi, Beverlyj Lange, Stella M. Davies

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Abstract

Purpose: FAS is a cell surface receptor involved in apoptotic signal transmission. Deregulation of this pathway results in down-regulation of apoptosis and subsequent persistence of a malignant clone. A single nucleotide polymorphism resulting in guanine-to-adenine transition in the FAS promoter region (position -1377) is thought to reduce stimulatoryprotein 1 transcription factor binding and decrease FAS expression. Previous work has shown increased risk of developing acute myeloid leukemia (AML) in adult patients with a variant allele at this site. The same authors have shown that the presence of an adenine residue rather than a guanine residue at -1,377 bp significantly attenuates transcription factor stimulatory protein 1 binding and may contribute to a reduction in FAS expression and ultimatelyto the enrichment of apoptosis-resistant clones in AML. We hypothesized that FAS genotype by altering susceptibility to apoptosis might affect outcome of childhood AML therapy. Experimental Design: Four hundred forty-four children treated for de novo AML on a uniform protocol were genotyped for FAS 1377. Results: There were no significant differences in overall survival, event-free survival, treatment- related mortality, or relapse rate between patients with FAS 1377GG genotype versus 1377GA/ 1377AA genotypes. Conclusions: FAS 1377 genotype does not alter outcome of de novo AML in children.

Original languageEnglish (US)
Pages (from-to)7896-7899
Number of pages4
JournalClinical Cancer Research
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2008

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    Mehta, P. A., Gerbing, R. B., Alonzo, T. A., Elliott, J. S., Zamzow, T., Combs, M., Stover, E., Ross, J. A., Perentesis, J. P., Meschinchi, S., Lange, B., & Davies, S. M. (2008). FAS promoter polymorphism: Outcome of childhood acute myeloid leukemia. A children's oncology group report. Clinical Cancer Research, 14(23), 7896-7899. https://doi.org/10.1158/1078-0432.CCR-08-0418