Meng Miaomiao, Feng Xiaoyan, Zhang Yue, Gao Yuyang, Han Lijuan, Li Zhaoming, Zhang Xudong, Zhang Mingzhi
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe Road, Zhengzhou, 450052, Henan, China.
The First Clinical Medical College of Zhengzhou University, Zhengzhou, Henan, China.
Ann Hematol. 2025 Mar;104(3):1747-1756. doi: 10.1007/s00277-025-06271-8. Epub 2025 Feb 27.
T-cell lymphoblastic lymphoma (T-LBL) has a poor response to traditional chemotherapy regimens, and is prone to relapse after treatment. Effective drugs are lacking for relapsed and refractory (RR) T-LBL patients, highlighting the need for novel treatments. Selinexor and decitabine have good effects on a variety of hematolymphatic diseases and solid tumors, but how effective they are in treating T-LBL has not been reported. In this study, we first investigated the efficacy and mechanism of selinexor combined with decitabine in the treatment of T- LBL.
The proliferation, apoptosis, and cell cycle progression of T-LBL cells were detected via CCK-8 and flow cytometry. Changes in mRNA expression and protein levels were assessed via mRNA sequencing, quantitative real-time PCR, and Western blotting. SLIT2 expression was detected by immunohistochemistry and Western blotting. Tumor xenograft models were established to evaluate the efficacy of drugs in vivo.
Selinexor or decitabine alone inhibited T-LBL cell proliferation in a dose-dependent manner. Cotreatment with both drugs had obvious synergistic effects, promoted cell apoptosis, and induced G0/G1-phase cell cycle arrest in T-LBL cells, and the RNA sequencing results indicated that the tumor suppressor gene SLIT2 might be involved in the synergistic effect of the two drugs. In vivo, this combination showed synergistic antitumor effects in xenograft mouse models.
In summary, selinexor in combination with decitabine has significant synergistic effects both in vitro and in vivo and represents a new treatment option for RR T-LBL.
T细胞淋巴母细胞淋巴瘤（T-LBL）对传统化疗方案反应不佳，且治疗后易复发。复发难治（RR）T-LBL患者缺乏有效的治疗药物，这凸显了新型治疗方法的必要性。塞利尼索和地西他滨对多种血液淋巴系统疾病和实体瘤有良好疗效，但它们在治疗T-LBL方面的效果尚未见报道。在本研究中，我们首先探讨了塞利尼索联合地西他滨治疗T-LBL的疗效及机制。
通过CCK-8和流式细胞术检测T-LBL细胞的增殖、凋亡和细胞周期进程。通过mRNA测序、定量实时PCR和蛋白质免疫印迹法评估mRNA表达和蛋白质水平的变化。通过免疫组织化学和蛋白质免疫印迹法检测SLIT2表达。建立肿瘤异种移植模型以评估药物在体内的疗效。
单独使用塞利尼索或地西他滨均以剂量依赖方式抑制T-LBL细胞增殖。两种药物联合治疗具有明显的协同作用，促进细胞凋亡，并诱导T-LBL细胞发生G0/G1期细胞周期阻滞，RNA测序结果表明肿瘤抑制基因SLIT2可能参与了两种药物的协同作用。在体内，这种联合用药在异种移植小鼠模型中显示出协同抗肿瘤作用。
综上所述，塞利尼索联合地西他滨在体外和体内均具有显著的协同作用，是RR T-LBL的一种新的治疗选择。
