Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury, UK.
Haematologica. 2010 Jan;95(1):148-52. doi: 10.3324/haematol.2009.011510.
Interferon alpha (IFN) induces variable responses in chronic myeloid leukemia (CML), with 8-30% of early chronic phase cases achieving a complete cytogenetic response. We hypothesized that polymorphic differences in genes encoding IFN signal transduction components might account for different patient responses. We studied 174 IFN-treated patients, of whom 79 achieved less than 35% Philadelphia-chromosome (Ph) positive metaphases (responders) and 95 failed to show any cytogenetic response (more than 95% Ph-positive metaphases; non-responders). We compared 17 single nucleotide polymorphisms (SNPs) at IFNAR1, IFNAR2, JAK1, TYK2, STAT1, STAT3 and STAT5a/b between the two groups and found a significant difference for rs6503691, a SNP tightly linked to STAT5a, STAT5b and STAT3 (minor allele frequency 0.16 for non-responders; 0.06 for responders, P=0.007). Levels of STAT3 mRNA correlated with rs6503691 genotype (P<0.001) as assessed by real time quantitative PCR and therefore we conclude that rs6503691 is associated with the STAT3 expression levels and response of CML patients to IFN.
干扰素 alpha（IFN）在慢性髓性白血病（CML）中引起不同的反应，8-30%的早期慢性期病例达到完全细胞遗传学反应。我们假设编码 IFN 信号转导成分的基因中的多态性差异可能导致不同的患者反应。我们研究了 174 名接受 IFN 治疗的患者，其中 79 名患者获得的费城染色体（Ph）阳性中期少于 35%（应答者），95 名患者未显示任何细胞遗传学反应（超过 95%的 Ph 阳性中期；无应答者）。我们比较了两组之间 IFNAR1、IFNAR2、JAK1、TYK2、STAT1、STAT3 和 STAT5a/b 中的 17 个单核苷酸多态性（SNP），发现 rs6503691 存在显著差异，rs6503691 与 STAT5a、STAT5b 和 STAT3 紧密连锁（非应答者的次要等位基因频率为 0.16；应答者为 0.06，P=0.007）。通过实时定量 PCR 评估，STAT3 mRNA 水平与 rs6503691 基因型相关（P<0.001），因此我们得出结论，rs6503691 与 CML 患者对 IFN 的 STAT3 表达水平和反应相关。
