The Role of Ptbp1 in T Cell Acute Lymphoblastic Leukemia Mice

doi:10.19586/j.2095-2341.2024.0182

Current Biotechnology ›› 2025, Vol. 15 ›› Issue (2): 341-348.DOI: 10.19586/j.2095-2341.2024.0182

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The Role of Ptbp1 in T Cell Acute Lymphoblastic Leukemia Mice

Xu ZHU¹(), Yingnan ZHANG¹, Jinfa MA¹, Lihong SHI¹^,²()

^1.State Key Laboratory of Experimental Hematology，National Clinical Research Center for Blood Disease，Haihe Laboratory of Cell Ecosystem，Institute of Hematology & Blood Diseases Hospital，Chinese Academy of Medical Sciences & Peking Union College，Tianjin 300020，China
^2.Tianjin Institutes of Health Science，Tianjin 301600，China

Received:2024-11-20 Accepted:2025-01-21 Online:2025-03-25 Published:2025-04-29
Contact: Lihong SHI

Ptbp1在小鼠急性T淋巴细胞白血病中的作用研究

朱旭¹(), 张英楠¹, 马金法¹, 石莉红¹^,²()

^1.中国医学科学院血液病医院（中国医学科学院血液学研究所），血液与健康全国重点实验室，国家血液系统疾病临床医学研究中心，细胞生态海河实验室，天津 300020
^2.天津医学健康研究院，天津 301600

通讯作者: 石莉红
作者简介:朱旭 E-mail: zhuxu@ihcams.ac.cn；
基金资助:
国家重点研发计划项目(2022YFA1103503);国家自然科学基金项目(82225003);中国医学科学院医学与健康科技创新工程项目(2023-I2M-007);细胞生态海河实验室“揭榜挂帅”项目(24HHXBSS00013);津门医学英才项目(TJSJMYXYC-D2-022);天津市科技计划项目(24ZXRKSY00010)

Abstract

Abstract:

The aim of this study is to explore the role of the classical RNA binding protein polypyrimidine bundle binding protein 1 （PTBP1） in the occurrence and development of T cell acute lymphoblastic leukemia （T-ALL）. Generating Mx1-Cre；Ptbp1^fl/fl mouse model that hematopoietic system specific knockout of Ptbp1 through Cre；Flox system. Mouse bone marrow lin^- cells were infected with Notch1 retrovirus， and the Ptbp1 knockout T-ALL model was established by transplantation experiments. The deletion of Ptbp1 was found to accelerate the disease progression of T-ALL， as indicated by a higher proportion of Notch1-GFP⁺ cells in the bone marrow of Ptbp1 knockout mice， suggesting faster disease progression. In addition， Ptbp1 knockout leukemia cells showed enhanced proliferation and decreased apoptosis， which was consistent with the rapid disease progression observed in mice. These results suggest the important role of Ptbp1 in the occurrence and development of T-ALL， and provide more understanding of Ptbp1 as a potential biomarker for T-ALL.

Key words: Ptbp1, T-ALL, mouse model, cell proliferation

摘要：

研究旨在探究经典的RNA结合蛋白多聚嘧啶束结合蛋白1（PTBP1）在急性T淋巴细胞白血病（T cell acute lymphoblastic leukemia，T-ALL）发生及发展中的作用。通过Cre;Flox系统，构建了在造血系统中特异性敲除Ptbp1的Mx1-Cre; Ptbp1^fl/fl小鼠模型，并利用Notch1的逆转录病毒感染小鼠原代骨髓lin^-细胞，通过移植实验，建立敲除Ptbp1的T-ALL疾病模型。研究发现Ptbp1的缺失加速了T-ALL的发展，表现为Ptbp1敲除组小鼠骨髓中Notch1-GFP⁺细胞比例更高，提示疾病发展速度更快。此外，Ptbp1敲除后的白血病细胞表现为增殖能力增强以及凋亡水平降低，这与小鼠体内实验观察到疾病快速进展相吻合。这些结果提示Ptbp1在T-ALL发生发展中的重要作用，为Ptbp1作为T-ALL潜在生物标志物提供了更多认识。

关键词: Ptbp1, T-ALL, 小鼠模型, 细胞增殖

CLC Number:

Q812

Xu ZHU, Yingnan ZHANG, Jinfa MA, Lihong SHI. The Role of Ptbp1 in T Cell Acute Lymphoblastic Leukemia Mice[J]. Current Biotechnology, 2025, 15(2): 341-348.

朱旭, 张英楠, 马金法, 石莉红. Ptbp1在小鼠急性T淋巴细胞白血病中的作用研究[J]. 生物技术进展, 2025, 15(2): 341-348.

Figures/Tables 5

Fig. 1 Construction of Ptbp1-Flox

Fig. 2 Flow chart of transplantation experiment

Fig. 3 The mouse model with specific knockout of Ptbp1 in the hematopoietic system

Fig. 4 Progression of T-ALL disease in Ptbp1 knockout mice

Fig. 5 Effects of knockout of Ptbp1 on the cell cycle and apotosis of T-ALL tumor cells in mouse

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The Role of Ptbp1 in T Cell Acute Lymphoblastic Leukemia Mice

Ptbp1在小鼠急性T淋巴细胞白血病中的作用研究

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