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.
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.
Authors: N Itoh; S Yonehara; A Ishii; M Yonehara; S Mizushima; M Sameshima; A Hase; Y Seto; S Nagata Journal: Cell Date: 1991-07-26 Impact factor: 41.582
Authors: Beverly J Lange; Robert B Gerbing; James Feusner; Jeffrey Skolnik; Nancy Sacks; Franklin O Smith; Todd A Alonzo Journal: JAMA Date: 2005-01-12 Impact factor: 56.272
Authors: D Delia; A Aiello; D Soligo; E Fontanella; C Melani; F Pezzella; M A Pierotti; G Della Porta Journal: Blood Date: 1992-03-01 Impact factor: 22.113
Authors: A Oehm; I Behrmann; W Falk; M Pawlita; G Maier; C Klas; M Li-Weber; S Richards; J Dhein; B C Trauth Journal: J Biol Chem Date: 1992-05-25 Impact factor: 5.157
Authors: F Rieux-Laucat; F Le Deist; C Hivroz; I A Roberts; K M Debatin; A Fischer; J P de Villartay Journal: Science Date: 1995-06-02 Impact factor: 47.728