Giannakoulas Angelos, Nikolaidis Marios, Amoutzias Grigorios D, Giannakoulas Nikolaos
Department of Hematology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
Bioinformatics Laboratory, Department of Biochemistry & Biotechnology, School of Health Sciences, University of Thessaly, Larissa, Greece.
Front Oncol. 2024 Apr 16;14:1390105. doi: 10.3389/fonc.2024.1390105. eCollection 2024.
Multiple myeloma (MM) is an incurable malignant plasma cell disorder characterized by the infiltration of clonal plasma cells in the bone marrow compartment. Gene Expression Profiling (GEP) has emerged as a powerful investigation tool in modern myeloma research enabling the dissection of the molecular background of MM and allowing the identification of gene products that could potentially serve as targets for therapeutic intervention. In this study we investigated shared transcriptomic abnormalities across newly diagnosed multiple myeloma (NDMM) patient cohorts. In total, publicly available transcriptomic data of 7 studies from CD138+ cells from 281 NDMM patients and 44 healthy individuals were integrated and analyzed. Overall, we identified 28 genes that were consistently differentially expressed (DE) between NDMM patients and healthy donors (HD) across various studies. Of those, 9 genes were over/under-expressed in more than 75% of NDMM patients. In addition, we identified 4 genes (MT1F, PURPL, LINC01239 and LINC01480) that were not previously considered to participate in MM pathogenesis. Meanwhile, by mining three drug databases (ChEMBL, IUPHAR/BPS and DrugBank) we identified 31 FDA-approved and 144 experimental drugs that target 8 of these 28 over/under-expressed MM genes. Taken together, our study offers new insights in MM pathogenesis and importantly, it reveals potential new treatment options that need to be further investigated in future studies.
多发性骨髓瘤（MM）是一种无法治愈的恶性浆细胞疾病，其特征是克隆性浆细胞浸润骨髓腔。基因表达谱分析（GEP）已成为现代骨髓瘤研究中的一种强大研究工具，能够剖析MM的分子背景，并识别可能作为治疗干预靶点的基因产物。在本研究中，我们调查了新诊断的多发性骨髓瘤（NDMM）患者队列中的共享转录组异常。总共整合并分析了来自281例NDMM患者和44例健康个体的CD138 +细胞的7项研究的公开可用转录组数据。总体而言，我们在各项研究中确定了28个基因，这些基因在NDMM患者和健康供体（HD）之间始终存在差异表达（DE）。其中，9个基因在超过75%的NDMM患者中过表达/低表达。此外，我们还确定了4个以前未被认为参与MM发病机制的基因（MT1F、PURPL、LINC01239和LINC01480）。同时，通过挖掘三个药物数据库（ChEMBL、IUPHAR/BPS和DrugBank），我们确定了31种FDA批准的和144种实验性药物，它们靶向这28个过表达/低表达的MM基因中的8个。综上所述，我们的研究为MM发病机制提供了新的见解，重要的是，它揭示了潜在的新治疗选择，需要在未来的研究中进一步研究。
