Satria Rahmat Dani, Irham Lalu Muhammad, Adikusuma Wirawan, Puspitaningrum Anisa Nova, Afief Arief Rahman, Khair Riat El, Septama Abdi Wira
Department of Clinical Pathology and Laboratory Medicine, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia.
Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta 55281, Indonesia.
Genomics Inform. 2023 Sep;21(3):e31. doi: 10.5808/gi.23011. Epub 2023 Sep 27.
Multiple myeloma (MM) is a hematological malignancy. It is widely believed that genetic factors play a significant role in the development of MM, as investigated in numerous studies. However, the application of genomic information for clinical purposes, including diagnostic and prognostic biomarkers, remains largely confined to research. In this study, we utilized genetic information from the Genomic-Driven Clinical Implementation for Multiple Myeloma database, which is dedicated to clinical trial studies on MM. This genetic information was sourced from the genome-wide association studies catalog database. We prioritized genes with the potential to cause MM based on established annotations, as well as biological risk genes for MM, as potential drug target candidates. The DrugBank database was employed to identify drug candidates targeting these genes. Our research led to the discovery of 14 MM biological risk genes and the identification of 10 drugs that target three of these genes. Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.
多发性骨髓瘤（MM）是一种血液系统恶性肿瘤。众多研究表明，人们普遍认为遗传因素在MM的发生发展中起着重要作用。然而，基因组信息在临床中的应用，包括诊断和预后生物标志物，在很大程度上仍局限于研究领域。在本研究中，我们利用了多发性骨髓瘤基因组驱动临床应用数据库中的遗传信息，该数据库专门用于MM的临床试验研究。这些遗传信息来源于全基因组关联研究目录数据库。我们根据既定注释对可能导致MM的基因以及MM的生物学风险基因进行了优先级排序，将其作为潜在的药物靶点候选基因。利用药物银行数据库来识别针对这些基因的候选药物。我们的研究发现了14个MM生物学风险基因，并确定了10种靶向其中3个基因的药物。值得注意的是，这10种药物中只有一种，即帕比司他，已被批准用于MM治疗。两种最具潜力的基因，钙信号调节亲环素配体（CAMLG）和组蛋白去乙酰化酶2（HDAC2），被4种药物（环孢素、贝利司他、伏立诺他和罗米地辛）靶向作用，所有这些药物都有临床证据支持其用于MM治疗。有趣的是，这10种药物中有5种已被批准用于MM以外的其他适应症，但它们也可能对MM治疗有效。因此，本研究旨在阐明MM发病机制中涉及的基因组变异，并突出这些基因组变异在药物发现中的潜在益处。
