| Autor: |
Xin Wu, Zhongguang Wu, Woding Deng, Rong Xu, Chunmei Ban, Xiaoying Sun, Qiangqiang Zhao |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-21 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
1479-5876 |
| DOI: |
10.1186/s12967-023-04579-5 |
| Popis: |
Abstract Background The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes. Methods To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations. Results Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149’s role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C. Conclusion In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149’s tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance. Graphical Abstract |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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