Devin Julie, Kassambara Alboukadel, Bruyer Angélique, Moreaux Jérôme, Bret Caroline
CNRS UMR9002, Institute of Human Genetics, 34090 Montpellier, France.
Department of Biological Hematology, St Eloi Hospital, 34295 Montpellier, France.
J Clin Med. 2019 Jul 22;8(7):1074. doi: 10.3390/jcm8071074.
Multiparameter flow cytometry (MFC) is a fast and cost-effective technique to evaluate the expression of many lymphoid markers in mature B-cell neoplasms, including diffuse large B cell lymphoma (DLBCL), which is the most frequent non-Hodgkin lymphoma. In this study, we first characterized by MFC the expression of 27 lymphoid markers in 16 DLBCL-derived cell lines to establish a robust algorithm for their authentication. Then, using the expression profile in DLBCL samples of the genes encoding B lymphoid markers that are routinely investigated by MFC, we built a gene expression-based risk score, based on the expression level of , and to predict the outcome of patients with DLBCL. This risk score allowed splitting patients in four risk groups, and was an independent predictor factor of overall survival when compared with the previously published prognostic factors. Lastly, to investigate the potential correlation between BCL2, BCL6, CD11c, and LAIR1 protein level and resistance to treatment, we investigated the response of the 16 DLBCL cell lines to cyclophosphamide, etoposide, doxorubicin, and gemcitabine. We found a correlation between BCL6 overexpression and resistance to etoposide. These results show the interest of MFC for the routine characterization of DLBCL cells and tumors samples for research and diagnostic/prognostic purposes.
多参数流式细胞术(MFC)是一种快速且经济高效的技术,可用于评估成熟B细胞肿瘤中多种淋巴样标志物的表达,包括弥漫性大B细胞淋巴瘤(DLBCL),这是最常见的非霍奇金淋巴瘤。在本研究中,我们首先通过MFC对16种DLBCL来源的细胞系中27种淋巴样标志物的表达进行了表征,以建立一种可靠的鉴定算法。然后,利用MFC常规检测的编码B淋巴样标志物的基因在DLBCL样本中的表达谱,我们基于、和的表达水平构建了一个基于基因表达的风险评分,以预测DLBCL患者的预后。该风险评分可将患者分为四个风险组,与先前公布的预后因素相比,它是总生存的独立预测因素。最后,为了研究BCL2、BCL6、CD11c和LAIR1蛋白水平与治疗耐药性之间的潜在相关性,我们研究了16种DLBCL细胞系对环磷酰胺、依托泊苷、阿霉素和吉西他滨的反应。我们发现BCL6过表达与对依托泊苷的耐药性之间存在相关性。这些结果表明MFC对于DLBCL细胞和肿瘤样本的常规表征在研究以及诊断/预后目的方面具有重要意义。