FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.
FAS promoter polymorphism: outcome of childhood acute myeloid leukemia. A children's oncology group report.
复制标题
DOI：
10.1158/1078-0432.ccr-08-0418
复制
发表时间：
2008-12-01
期刊：
影响因子：
--
通讯作者：
Davies SM
中科院分区：
文献类型：
--
作者：
Mehta PA;Gerbing RB;Alonzo TA;Elliott JS;Zamzow TA;Combs M;Stover E;Ross JA;Perentesis JP;Meschinchi S;Lange BJ;Davies SM
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 (G→A) transition in the FAS promoter region (position –1377) is thought to reduce stimulatory protein 1 (SP1) 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 –1377 bp significantly attenuates transcription factor SP1 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 impact outcome of childhood AML therapy. 440 children treated for de novo AML on a uniform protocol were genotyped for FAS 1377. There were no significant differences in overall survival (OS), event-free survival (EFS), treatment-related mortality (TRM), or relapse rate between patients with FAS 1377GG genotype vs. 1377GA/1377AA genotypes. FAS1377 genotype does not alter outcome of de novo AML in children.
