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FAS Promoter Polymorphism: Outcome of Childhood Acute Myeloid Leukemia. A Children's Oncology Group Report

Authors' Affiliations: ¹ Division of Hematology/Oncology, Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio; ² University of Southern California Keck School of Medicine, Los Angeles, California; ³ Children's Oncology Group, Arcadia, California; ⁴ Department of Pediatrics, University of Minnesota Cancer Center, Minneapolis, Minnesota; ⁵ Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; and ⁶ Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

Requests for reprints: Parinda A. Mehta, Division of Hematology/Oncology, Cincinnati Children's Hospital and Medical Center, MLC 7015, 3333 Burnet Avenue, Cincinnati, OH 45229. Phone: 513-636-4913; Fax: 513-636-3549; E-mail: parinda.mehta{at}cchmc.org.

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 stimulatory protein 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 ultimately to 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.