| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Zhu, Xiao-Na Wei, Yu-Sheng Yang, Qian Liu, Hao-Ran Zhi, Zhe Zhu, Di Xia, Li Hong, Deng-Li Yu, Yun Chen, Guo-Qiang |
| Abstract | Background Selectively targeting leukemia stem cells (LSCs) is a promising approach in treating acute myeloid leukemia (AML), for which identification of such therapeutic targets is critical. Increasing lines of evidence indicate that FBXO22 plays a critical role in solid tumor development and therapy response. However, its potential roles in leukemogenesis remain largely unknown. Methods We established a mixed lineage leukemia (MLL)-AF9-induced AML model with hematopoietic cell-specific FBXO22 knockout mice to elucidate the role of FBXO22 in AML progression and LSCs regulation, including self-renewal, cell cycle, apoptosis and survival analysis. Immunoprecipitation combined with liquid chromatography-tandem mass spectrometry analysis, Western blotting and rescue experiments were performed to study the mechanisms underlying the oncogenic role of FBXO22. Results FBXO22 was highly expressed in AML, especially in MLL-rearranged (MLLr) AML. Upon FBXO22 knockdown, human MLLr leukemia cells presented markedly increased apoptosis. Although conditional deletion of Fbxo22 in hematopoietic cells did not significantly affect the function of hematopoietic stem cells, MLL-AF9-induced leukemogenesis was dramatically abrogated upon Fbxo22 deletion, together with remarkably reduced LSCs after serial transplantations. Mechanistically, FBXO22 promoted degradation of BACH1 in MLLr AML cells, and overexpression of BACH1 suppressed MLLr AML progression. In line with this, heterozygous deletion of BACH1 significantly reversed delayed leukemogenesis in Fbxo22-deficient mice. Conclusions FBXO22 promotes MLLr AML progression by targeting BACH1 and targeting FBXO22 might be an ideal strategy to eradicate LSCs without influencing normal hematopoiesis. |
| Related Links | https://jhoonline.biomedcentral.com/counter/pdf/10.1186/s13045-023-01400-0.pdf |
| Ending Page | 22 |
| Page Count | 22 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17568722 |
| DOI | 10.1186/s13045-023-01400-0 |
| Journal | Journal of Hematology & Oncology |
| Issue Number | 1 |
| Volume Number | 16 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2023-02-11 |
| Access Restriction | Open |
| Subject Keyword | Oncology Hematology Cancer Research FBXO22 Leukemia stem cells (LSCs) Acute myeloid leukemia (AML) BTB and CNC homology 1 (BACH1) |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hematology Cancer Research Oncology Molecular Biology |
| Journal Impact Factor | 29.9/2023 |
| 5-Year Journal Impact Factor | 27.1/2023 |
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