Gimondi Silvia, Dugo Matteo, Vendramin Antonio, Bermema Anisa, Biancon Giulia, Cavané Alessandra, Corradini Paolo, Carniti Cristiana
Department of Hematology and Pediatric Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; Department of Hematology, Department of Oncology and Onco-Hematology, Università degli Studi di Milano, Milan, Italy.
Functional Genomics Core Facility, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Exp Hematol. 2016 Jul;44(7):624-634.e1. doi: 10.1016/j.exphem.2016.03.005. Epub 2016 Mar 21.
Acute graft-versus-host disease (aGVHD) results in significant morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Noninvasive diagnostic and prognostic tests for aGVHD are currently lacking, but would be beneficial in predicting aGVHD and improving the safety of allo-HSCT. Circulating microRNAs exhibit marked stability and may serve as biomarkers in several clinical settings. Here, we evaluated the use of circulating microRNAs as predictive biomarkers of aGVHD in lymphoma patients after allo-HSCT from matched unrelated donors (MUDs). After receiving informed consent, we prospectively collected plasma samples from 24 lymphoma patients before and after unmanipulated MUD allo-HSCT; microRNAs were then isolated. Fourteen patients developed aGVHD symptoms at a median of 48 days (range: 32-90) post-transplantation. Two patients developed intestinal GVHD, eight cutaneous GVHD, and four multiorgan GVHD. The microRNA expression profile was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MicroRNAs 194 and 518f were significantly upregulated in aGVHD samples compared with samples taken from non-aGVHD patients. Remarkably, these upregulated microRNAs could be detected before the onset of aGVHD. Pathway prediction analysis indicated that these microRNAs may regulate critical pathways involved in aGVHD pathogenesis. Considering the noninvasive characteristics of plasma sampling and the feasibility of detecting miRNAs after allo-HSCT using real-time polymerase chain reaction, our results indicate that circulating microRNAs have the potential to enable an earlier aGVHD diagnosis and might assist in individualizing therapeutic strategies after MUD allo-HSCT. Nevertheless, standardization of blood sampling and analysis protocols is mandatory for the introduction of miRNA profiling into routine clinical use.
急性移植物抗宿主病（aGVHD）在异基因造血干细胞移植（allo-HSCT）后会导致显著的发病率和死亡率。目前缺乏针对aGVHD的非侵入性诊断和预后检测方法，但这对于预测aGVHD以及提高allo-HSCT的安全性将是有益的。循环微小RNA表现出显著的稳定性，并且在多种临床情况下可能作为生物标志物。在此，我们评估了循环微小RNA作为来自匹配无关供体（MUDs）的allo-HSCT后淋巴瘤患者aGVHD预测生物标志物的用途。在获得知情同意后，我们前瞻性地收集了24例淋巴瘤患者在未处理的MUD allo-HSCT前后的血浆样本；随后分离出微小RNA。14例患者在移植后中位48天（范围：32 - 90天）出现aGVHD症状。2例患者发生肠道GVHD，8例发生皮肤GVHD，4例发生多器官GVHD。使用定量实时聚合酶链反应（qRT-PCR）检测微小RNA表达谱。与非aGVHD患者的样本相比，微小RNA 194和518f在aGVHD样本中显著上调。值得注意的是，这些上调的微小RNA在aGVHD发作之前就能被检测到。通路预测分析表明，这些微小RNA可能调节参与aGVHD发病机制的关键通路。考虑到血浆采样的非侵入性特征以及使用实时聚合酶链反应在allo-HSCT后检测微小RNA的可行性，我们的结果表明循环微小RNA有潜力实现aGVHD的早期诊断，并可能有助于在MUD allo-HSCT后制定个体化治疗策略。然而，将微小RNA谱分析引入常规临床应用时，血液采样和分析方案的标准化是必不可少的。
