Martins Juliana Ravelli Baldassarre, de Moraes Leonardo Nazario, Cury Sarah Santiloni, Dadalto Juliane, Capannacci Juliana, Carvalho Robson Francisco, Nogueira Célia Regina, Hokama Newton Key, Hokama Paula de Oliveira Montandon
Department of Internal Medicine, São Paulo State University (UNESP-FMB), Botucatu, Brazil.
Department of Bioprocesses and Biotechnology, São Paulo State University (UNESP-FCA), Botucatu, Brazil.
Front Oncol. 2020 Sep 4;10:1544. doi: 10.3389/fonc.2020.01544. eCollection 2020.
Chronic myeloid leukemia (CML) results from a translocation between chromosomes 9 and 22, which generates the Philadelphia chromosome. This forms BCR/ABL1, an active tyrosine kinase protein that promotes cell growth and replication. Despite great progress in CML treatment in the form of tyrosine kinase inhibitors, allogeneic-hematopoietic stem cell transplantation (allo-HSCT) is currently used as an important treatment alternative for patients resistant to these inhibitors. Studies have shown that unregulated expression of microRNAs, which act as oncogenes or tumor suppressors, is associated with human cancers. This contributes to tumor formation and development by stimulating proliferation, angiogenesis, and invasion. Research has demonstrated the potential of microRNAs as biomarkers for cancer diagnosis, prognosis, and therapeutic targets. In the present study, we compared the circulating microRNA expression profiles of 14 newly diagnosed patients with chronic phase-CML and 14 Philadelphia chromosome-negative patients after allo-HSCT. For each patient, we tested 758 microRNAs by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis. The global expression profile of microRNAs revealed 16 upregulated and 30 downregulated microRNAs. Target genes were analyzed, and key pathways were extracted and compared. Bioinformatics tools were used to analyze data. Among the downregulated miRNA target genes, some genes related to cell proliferation pathways were identified. These results reveal the comprehensive microRNA profile of CML patients and the main pathways related to the target genes of these miRNAs in cytogenetic remission after allo-HSCT. These results provide new resources for exploring stem cell transplantation-based CML treatment strategies.
慢性髓性白血病(CML)源于9号和22号染色体之间的易位,产生了费城染色体。这形成了BCR/ABL1,一种促进细胞生长和复制的活性酪氨酸激酶蛋白。尽管酪氨酸激酶抑制剂形式的CML治疗取得了巨大进展,但异基因造血干细胞移植(allo-HSCT)目前被用作对这些抑制剂耐药患者的重要治疗选择。研究表明,作为癌基因或肿瘤抑制因子的微小RNA的失控表达与人类癌症有关。这通过刺激增殖、血管生成和侵袭促进肿瘤形成和发展。研究已经证明了微小RNA作为癌症诊断、预后和治疗靶点生物标志物的潜力。在本研究中,我们比较了14例新诊断的慢性期CML患者和14例allo-HSCT后费城染色体阴性患者的循环微小RNA表达谱。对于每位患者,我们通过逆转录定量聚合酶链反应(RT-qPCR)分析检测了758种微小RNA。微小RNA的整体表达谱显示16种上调和30种下调的微小RNA。对靶基因进行了分析,并提取和比较了关键途径。使用生物信息学工具分析数据。在下调的miRNA靶基因中,鉴定出一些与细胞增殖途径相关的基因。这些结果揭示了CML患者的综合微小RNA谱以及allo-HSCT后细胞遗传学缓解中这些miRNA靶基因相关的主要途径。这些结果为探索基于干细胞移植的CML治疗策略提供了新的资源。