课题基金基金详情
胞浆p27Kip1蛋白经非常规途径分泌的分子机制及其在儿童急性淋巴细胞白血病复发与耐药中作用的研究
结题报告
批准号:
81970135
项目类别:
面上项目
资助金额:
55.0 万元
负责人:
崔蕾
依托单位:
学科分类:
白血病
结题年份:
2023
批准年份:
2019
项目状态:
已结题
项目参与者:
崔蕾
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中文摘要
复发与耐药是进一步提高儿童急性淋巴细胞白血病(ALL)疗效、改善预后的主要障碍。我们的前期研究发现,胞浆p27Kip1蛋白增多与儿童ALL复发、耐药相关;白血病细胞的胞浆 p27Kip1蛋白可经非常规途径分泌并在细胞间传递,因而推测ALL细胞通过胞浆p27Kip1分泌与传递,导致耐药性增加。拟从分子、细胞及动物水平,明确p27Kip1与白血病细胞膜上关键结合蛋白LRP1B特异性结合并启动细胞内吞的分子机制,并证明摄入胞浆的p27Kip1通过与PRDX1相互作用,激活EMT通路及增强白血病细胞干性,从而导致白血病细胞耐药与复发。创新点是首次发现并探索了白血病细胞中p27Kip1分泌并进行细胞间传递的分子机制,创新性地从蛋白质分泌、细胞间相互影响的角度,来探讨儿童ALL中胞浆p27Kip1增多导致耐药、复发的机制,为相关研究开拓新的思路,并为复发/难治性患儿探寻新的治疗靶点提供理论依据。
英文摘要
Relapse and chemoresistance remain to be the major obstacle for improving the treatment outcome of childhood acute lymphoblastic leukemia (ALL). We have found that increase of cytoplasmic p27Kip1 was associated with relapse and chemoresistance, and cytoplasmic p27Kip1 of leukemia cells could be secreted by unconventional pathway and transferred between cells. Based on these results, we proposed a hypothesis that secretion and transmission of cytoplasmic p27Kip1 in ALL cells could lead to increase of chemoresistance of leukemia cells. We plan to carry out studies at molecular, cellular, and experimental animal levels as follows: cytoplasmic p27Kip1 transmission could be initiated by binding LRP1B on plasma membrane. Intake of p27Kip1 in cytoplasm could activate EMT pathway and enhance leukemic cell stemness by interacting with PRDX1, which would lead to drug resistance and relapse. The innovation of this study is to explore for the first time the mechanism of p27Kip1 secretion and transmission in leukemia cells. The mechanism of chemoresistance and relapse caused by the increase of cytoplasmic p27Kip1 in childhood ALL will be explored innovatively from the perspective of protein secretion and interaction between leukemia cells. This study will be of great help to open up new ideas for relevant research and provide theoretical basis for finding new therapeutic targets for relapsed or refractory patients with childhood ALL.
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Combined analysis ofIKZF1deletions andCRLF2expression on prognostic impact in pediatric B-cell precursor acute lymphoblastic leukemia
IKZF1 缺失和 CRLF2 表达对儿童 B 细胞前体急性淋巴细胞白血病预后影响的联合分析
DOI:10.1080/10428194.2020.1832668
发表时间:2020-10-13
期刊:LEUKEMIA & LYMPHOMA
影响因子:2.6
作者:Cui, Lei;Gao, Chao;Zhang, Rui-Dong
通讯作者:Zhang, Rui-Dong
Interaction of E2F3a and CASP8AP2 Regulates Histone Expression and Chemosensitivity of Leukemic Cells.
E2F3a 和 CASP8AP2 的相互作用调节白血病细胞的组蛋白表达和化疗敏感性
DOI:10.1097/mph.0000000000002558
发表时间:2023-04-01
期刊:JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
影响因子:1.2
作者:Jin, Fen-fen;Wang, Chan-juan;Cui, Lei;Liu, Fei-fei;Wang, Kai-ling;Li, Wei-jing;Li, Zhi-gang
通讯作者:Li, Zhi-gang
DOI:--
发表时间:2023
期刊:中国小儿血液与肿瘤杂志
影响因子:--
作者:黄筱彤;李志刚;崔蕾
通讯作者:崔蕾
Low expression ofCTBP2andCASP8AP2predicts risk of relapse in childhood B-cell precursor acute lymphoblastic leukemia: a retrospective cohort study
CTBP2和CASP8AP2的低表达可预测儿童B细胞前体急性淋巴细胞白血病的复发风险:一项回顾性队列研究
DOI:10.1080/08880018.2020.1798572
发表时间:2020
期刊:Pediatric Hematology and Oncology
影响因子:1.7
作者:Cui Lei;Gao Chao;Wang Chan-Juan;Liu Shu-Guang;Wu Min-Yuan;Zhang Rui-Dong;Li Zhi-Gang
通讯作者:Li Zhi-Gang
DOI:10.1080/08880018.2022.2033369
发表时间:2022-02
期刊:Pediatric Hematology and Oncology
影响因子:1.7
作者:Chan-Juan Wang;M.-Z Jia;Lingli Deng;Weijing Li;Qing Zhang;Tong-Jia Zhang;Shu-Yan Li;L. Cui;Zhigang Li
通讯作者:Chan-Juan Wang;M.-Z Jia;Lingli Deng;Weijing Li;Qing Zhang;Tong-Jia Zhang;Shu-Yan Li;L. Cui;Zhigang Li
CASP8AP2与ARS2相互作用参与microRNA-210生成及其在儿童急性淋巴细胞白血病复发与耐药中的作用
  • 批准号:
    81200392
  • 项目类别:
    青年科学基金项目
  • 资助金额:
    23.0万元
  • 批准年份:
    2012
  • 负责人:
    崔蕾
  • 依托单位:
国内基金
海外基金