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蛋白酪氨酸磷酸酶非受体型21通过生长停滞和DNA损伤诱导蛋白45α及应激活化蛋白激酶信号通路抑制化疗药物诱导的急性淋巴细胞白血病细胞凋亡。

PTPN21 inhibits cell apoptosis of acute lymphoblastic leukemia induced by chemotherapeutic agents via GADD45A and JNK signaling pathway.

作者信息

Zhao Chenze, Zhang Yu, Huang Linlin, Xiang Jingjing, Ye Baodong, Zhu Ni

机构信息

Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.

Department of Hematology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang, China.

出版信息

PLoS One. 2025 Apr 30;20(4):e0322273. doi: 10.1371/journal.pone.0322273. eCollection 2025.

Abstract

Acute lymphoblastic leukemia (ALL), a hematologic malignancy characterized by the uncontrolled proliferation of immature lymphocytes, often results in unfavorable long-term survival prospects for patients. PTPN21, a protein with established roles in oncogenesis, has been implicated in the pathogenesis of ALL. This study explores the role of PTPN21 in ALL cell apoptosis induced by chemotherapeutic agents. Key findings reveal that elevated PTPN21 levels hinder the apoptosis of ALL cells in response to vincristine (VCR) and daunorubicin (DNR). PTPN21 accomplishes this by inhibiting the GADD45A and JNK signaling pathways, thereby reversing cell cycle arrest in the G2/M phase. Restoring GADD45A reverses the anti-apoptotic effect of PTPN21. These findings suggest that targeting PTPN21 in conjunction with chemotherapy may represent a novel therapeutic strategy for ALL, offering potential implications for improving treatment efficacy and overcoming drug resistance.

摘要

急性淋巴细胞白血病(ALL)是一种血液系统恶性肿瘤,其特征为未成熟淋巴细胞的不受控制增殖,常常导致患者长期生存前景不佳。PTPN21是一种在肿瘤发生中已明确具有作用的蛋白质,与ALL的发病机制有关。本研究探讨了PTPN21在化疗药物诱导的ALL细胞凋亡中的作用。主要发现表明,PTPN21水平升高会阻碍ALL细胞对长春新碱(VCR)和柔红霉素(DNR)的凋亡反应。PTPN21通过抑制GADD45A和JNK信号通路来实现这一点,从而逆转细胞周期在G2/M期的阻滞。恢复GADD45A可逆转PTPN21的抗凋亡作用。这些发现表明,在化疗的同时靶向PTPN21可能代表一种针对ALL的新型治疗策略,对提高治疗效果和克服耐药性具有潜在意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/60c2/12043166/695a45583273/pone.0322273.g001.jpg

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