Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients.
Low Socioeconomic Status, Adverse Gene Expression Profiles, and Clinical Outcomes in Hematopoietic Stem Cell Transplant Recipients.
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DOI：
10.1158/1078-0432.ccr-15-1344
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Cole SW
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文献类型：
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作者：
Knight JM;Rizzo JD;Logan BR;Wang T;Arevalo JM;Ma J;Cole SW
低社会经济地位（SES）与无关供体造血干细胞移植（HCT）受者的不良结局相关，但导致这种健康差异的生物学机制尚不清楚。因此，我们研究了社会环境是否会影响应激相关基因表达谱的表达，即逆境保守转录反应（CTRA），其中包括促炎基因的上调和I型IFN反应和抗体合成相关基因的下调。我们比较了一组78例首次缓解的急性髓细胞性白血病非亲缘供者HCT的高SES与低SES受者之间的移植前白细胞CTRA基因表达。事后探索性分析还评估了CTRA基因表达是否与不良临床结局相关。与匹配的高SES HCT受体相比，从低SES个体中收集的HCT前外周血单核细胞显示出显著的CTRA上调。基于启动子的生物信息学暗示了转录因子活性的不同模式，包括CREB信号的增加和IRF和GR信号的减少。CTRA基因的高表达也与复发风险增加和无白血病生存率降低相关。低SES与CTRA基因表达谱的增加相关，CTRA基因表达与不利的HCT临床结果相关。这些发现提供了一个生物学框架，在此框架内了解社会环境条件如何影响同种异体HCT的免疫功能和临床结局。
Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I IFN response and antibody synthesis. We compared pre-transplant leukocyte CTRA gene expression between a group of 78 high vs. low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA up-regulation compared to matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT.