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Multiple myeloma (MM) is a genetically complex disease that results from a multistep transformation of normal to malignant plasma cells in the bone marrow. However, the molecular mechanisms responsible for the initiation and heterogeneous evolution of MM remain largely unknown. A fundamental step needed to understand the oncogenesis of MM and its response to therapy is the identification of driver mutations. The introduction of gene expression profiling (GEP) in MM is an important step in elucidating the molecular heterogeneity of MM and its clinical relevance. Since some mutations in myeloma occur in non-coding regions, studies based on the analysis of mRNA provide more comprehensive information on the oncogenic pathways and mechanisms relevant to MM biology. In this review, we discuss the role of gene expression profiling in understanding the biology of multiple myeloma together with the clinical manifestation of the disease, as well as its impact on treatment decisions and future directions.

多發(fā)性骨髓瘤 (MM) 是一種遺傳復(fù)雜的疾病，由骨髓中正常漿細(xì)胞向惡性漿細(xì)胞的多步轉(zhuǎn)化引起。然而，負(fù)責(zé) MM 的起始和異質(zhì)進(jìn)化的分子機(jī)制在很大程度上仍然未知。了解 MM 的發(fā)生及其對治療的反應(yīng)所需的一個基本步驟是識別驅(qū)動突變。在 MM 中引入基因表達(dá)譜 (GEP) 是闡明 MM 的分子異質(zhì)性及其臨床相關(guān)性的重要一步。由于骨髓瘤的一些突變發(fā)生在非編碼區(qū)，基于 mRNA 分析的研究提供了關(guān)于與 MM 生物學(xué)相關(guān)的致癌途徑和機(jī)制的更全面的信息。

40層細(xì)胞工廠

             Gene expression profiling studies provide important information regarding the biology of multiple myeloma and may serve as a tool to predict outcomes and guide therapy. In the era of personalized medicine, the future lies in enabling therapy to be chosen based on the presence of specific mutations and gene expression profiles. However, the complexity of the MM genome and transcriptome still requires further investigation.
          在回顧信使 RNA 在多發(fā)性骨髓瘤生物學(xué)中的作用時，重要的是包括嵌合抗原受體 (CAR) T 細(xì)胞療法領(lǐng)域的最新成果。盡管引入了許多新的治療策略，但多發(fā)性骨髓瘤仍然無法治愈，需要持續(xù)干預(yù)以控制疾病。然而，最近的一個有希望的發(fā)展是設(shè)計了一種工程化的 T 細(xì)胞產(chǎn)品 Descartes-08，它用抗 B 細(xì)胞成熟抗原 (BCMA) CAR mRNA 瞬時修飾自體 CD8 + T 細(xì)胞的純化群體，如報道林等人。

         A.P. wrote the paper. A.P., P.R., T.R. and D.M. examined the available data, reviewed, and revised the manuscript and provided their approval of the final version of the manuscript. All authors agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.
         Descartes-08 是通過 mRNA 轉(zhuǎn)染設(shè)計的，可以在規(guī)定的時間內(nèi)表達(dá)抗 BCMA CAR。mRNA 是通過線性化 DNA 質(zhì)粒的體外轉(zhuǎn)錄合成的 [ 78]。這種無病毒 CAR-T 細(xì)胞技術(shù)的發(fā)展最近導(dǎo)致了第一次臨床試驗的啟動。

 
T75細(xì)胞培養(yǎng)方瓶

biology; drug resistance; gene expression profiling; mRNA; multiple myeloma; prognosis; treatment

生物學(xué)；耐藥性；基因表達(dá)譜；mRNA ; 多發(fā)性骨髓瘤；預(yù)后；治療

來源：MDPI https://www.mdpi.com/1422-0067/22/21/12070/htm