Experimental Hematology Lab, IIS-Fundación Jimenez Díaz, UAM, Madrid, Spain.
Department of Chemistry in Pharmaceutical Sciences, School of Pharmacy, Universidad Complutense de Madrid, UCM, Instituto Investigación Sanitaria Hospital 12 de Octubre, Madrid, Spain.
Leuk Lymphoma. 2022 Aug;63(8):1861-1870. doi: 10.1080/10428194.2022.2056173. Epub 2022 Apr 4.
Activated B-cell (ABC) lymphoma, a distinct molecular entity within diffuse large B-cell lymphoma (DLBCL), remains highly incurable, showing a worse response to standard immunochemotherapy. The discouraging results obtained in several clinical trials using proteasome inhibitors, tyrosine kinase inhibitors, or immunomodulators, lead to an intense search for new, potentially druggable biomarkers in DLBCL. In this study, we designed an experimental strategy for DLBCL to discover high- and low-abundance RNA-seq-derived transcripts involved in the oncogenic phenotype in patients diagnosed with ABC-DLBCL. Based on the results of a comparative analysis, 79 DE genes and two enriched gene sets related to metabolism and immunity were selected. Genes related to drug resistance, anti-inflammatory response, and tumor-cell dissemination were found to be up-regulated, while tumor suppressor genes were down-regulated. Then, we searched for the perturbagens most suitable for gene expression profiling (GEP) by iLINCS-CMap. Herein, we present a novel experimental approach that connects the omics signature of DLBCL with potential drugs for more accurate treatments.
活化 B 细胞（ABC）淋巴瘤是弥漫性大 B 细胞淋巴瘤（DLBCL）中的一个独特分子实体，仍然高度难以治愈，对标准免疫化疗的反应更差。在使用蛋白酶体抑制剂、酪氨酸激酶抑制剂或免疫调节剂的几项临床试验中获得的令人沮丧的结果，促使人们在 DLBCL 中寻找新的、潜在可用药的生物标志物。在这项研究中，我们设计了一种针对 DLBCL 的实验策略，以发现与诊断为 ABC-DLBCL 的患者的致癌表型相关的高丰度和低丰度 RNA-seq 衍生转录本。基于比较分析的结果，选择了 79 个差异表达基因和两个与代谢和免疫相关的富集基因集。发现与耐药性、抗炎反应和肿瘤细胞扩散相关的基因上调，而肿瘤抑制基因下调。然后，我们通过 iLINCS-CMap 搜索最适合基因表达谱（GEP）的扰动剂。在此，我们提出了一种新的实验方法，将 DLBCL 的组学特征与潜在药物联系起来，以进行更准确的治疗。
