CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
靶向 CARM1 损害 DNA 损伤修复并减轻 B 细胞急性淋巴细胞白血病进展
英文原题：Targeting CARM1 impairs DNA damage repair and attenuates B-cell acute lymphoblastic leukemia progression.
查看英文原题
Targeting CARM1 impairs DNA damage repair and attenuates B-cell acute lymphoblastic leukemia progression.
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中文摘要
B细胞急性淋巴细胞白血病（B-ALL）是一种常见的血液系统恶性肿瘤，难治性和复发性患者难以找到有效的治疗策略。我们的研究发现，共激活因子相关精氨酸甲基转移酶1（CARM1）在B-ALL中高表达，并与不良预后相关。下调和抑制CARM1可有效抑制B-ALL的增殖和集落形成，同时诱导凋亡和细胞周期阻滞。在机制上，抑制或下调CARM1可降低PARP1水平并促进双链断裂（DSBs）的积累。抑制CARM1和PARP1可协同抑制B-ALL的发展。值得注意的是，抑制CARM1可促进记忆分化并减少CD19-CAR-T 细胞的耗竭。综上所述，抑制CARM1不仅可抑制B-ALL，还可增强CAR-T 细胞对抗B-ALL的持久性，这为CARM1抑制在肿瘤治疗中的抑瘤作用和免疫调节提供了新的见解。
展开英文摘要原文
B-cell acute lymphoblastic leukemia (B-ALL) is a prevalent hematological malignancy, posing difficulties in identifying efficacious treatment strategies for refractory and recurrent patients.
Our research revealed that coactivator-associated arginine methyltransferase 1 (CARM1) was highly expressed in B-ALL and associated with unfavorable prognostic outcomes. Down-regulation and inhibition of CARM1 effectively suppressed proliferation and colony formation of B-ALL, while also inducing apoptosis and cell cycle arrest.
Mechanistically, inhibition or down-regulation of CARM1 reduced PARP1 level and contributed to double-strand breaks (DSBs) accumulation. Inhibition of CARM1 and PARP1 synergistically supressed B-ALL development. Significantly, the inhibition of CARM1 was found to promote memory differentiation and reduce the exhaustion of CD19-CAR-T cells.
Taken together, CARM1 inhibition not only suppressed B-ALL but also enhanced the durability of CAR-T cells against B-ALL, which provides novel insights into the tumor suppression and immune regulation of CARM1 inhibition on cancer therapy.
论文信息
- 作者
- Liao P、Qiu Y、Li M、Hu R、Wang H、Zhang H、Wu S、Liang Z
- 第一作者单位
- Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.China
- 通讯作者单位
- Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China; Guangdong Engineering Research Center of Precision Immune Cell Therapy Technology, Guangzhou, China. Electronic address: liyuhua1974@outlook.com.China
- 期刊
- Biochimica et biophysica acta. Molecular basis of disease2026 Aug 30
- 原文标识
- PubMed 42669369 · DOI 10.1016/j.bbadis.2026.168444