FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML
Acute myeloid leukemia (AML) is an aggressive hematological malignancy that recurs in approximately 50% of cases. Elevated homing and uncontrolled expansion are characteristics of AML cells. Here, we identified that Fifth Ewing Variant (FEV) regulates the homing and expansion of AML cells. We found...
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| Format: | Article |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.890346/full |
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| author | Jubin Zhang Jubin Zhang Lijuan Qi Lijuan Qi Tanzhen Wang Tanzhen Wang Jingnan An Jingnan An Biqi Zhou Biqi Zhou Yanglan Fang Yanglan Fang Yujie Liu Yujie Liu Meng Shan Meng Shan Dengli Hong Depei Wu Depei Wu Yang Xu Yang Xu Tianhui Liu Tianhui Liu |
| author_facet | Jubin Zhang Jubin Zhang Lijuan Qi Lijuan Qi Tanzhen Wang Tanzhen Wang Jingnan An Jingnan An Biqi Zhou Biqi Zhou Yanglan Fang Yanglan Fang Yujie Liu Yujie Liu Meng Shan Meng Shan Dengli Hong Depei Wu Depei Wu Yang Xu Yang Xu Tianhui Liu Tianhui Liu |
| author_sort | Jubin Zhang |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) is an aggressive hematological malignancy that recurs in approximately 50% of cases. Elevated homing and uncontrolled expansion are characteristics of AML cells. Here, we identified that Fifth Ewing Variant (FEV) regulates the homing and expansion of AML cells. We found that FEV was re-expressed in 30% of primary AML samples and in almost all relapsed AML samples, and FEV expression levels were significantly higher in relapsed samples compared to primary samples. Interference of FEV expression in AML cell lines delayed leukemic progression and suppressed homing and proliferation. Moreover, FEV directly activated integrin subunit alpha 4 (ITGA4) transcription in a dose-dependent manner. Inhibition of integrin α4 activity with natalizumab (NZM) reduced the migration and colony-forming abilities of blasts and leukemic-initiating cells (LICs) in both primary and relapsed AML. Thus, our study suggested that FEV maintains the homing and expansion of AML cells by activating ITGA4 transcription and that targeting ITGA4 inhibits the colony-forming and migration capacities of blasts and LICs. Thus, these findings suggested that the FEV-ITGA4 axis may be a therapeutic target for both primary and relapsed AML. |
| first_indexed | 2024-12-11T15:40:19Z |
| format | Article |
| id | doaj.art-acfc6d7b85f241ecaf45dfa0f2d724d4 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-11T15:40:19Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-acfc6d7b85f241ecaf45dfa0f2d724d42022-12-22T00:59:49ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.890346890346FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AMLJubin Zhang0Jubin Zhang1Lijuan Qi2Lijuan Qi3Tanzhen Wang4Tanzhen Wang5Jingnan An6Jingnan An7Biqi Zhou8Biqi Zhou9Yanglan Fang10Yanglan Fang11Yujie Liu12Yujie Liu13Meng Shan14Meng Shan15Dengli Hong16Depei Wu17Depei Wu18Yang Xu19Yang Xu20Tianhui Liu21Tianhui Liu22National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaKey Laboratory of Cell Differentiation and Apoptosis of Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaNational Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaAcute myeloid leukemia (AML) is an aggressive hematological malignancy that recurs in approximately 50% of cases. Elevated homing and uncontrolled expansion are characteristics of AML cells. Here, we identified that Fifth Ewing Variant (FEV) regulates the homing and expansion of AML cells. We found that FEV was re-expressed in 30% of primary AML samples and in almost all relapsed AML samples, and FEV expression levels were significantly higher in relapsed samples compared to primary samples. Interference of FEV expression in AML cell lines delayed leukemic progression and suppressed homing and proliferation. Moreover, FEV directly activated integrin subunit alpha 4 (ITGA4) transcription in a dose-dependent manner. Inhibition of integrin α4 activity with natalizumab (NZM) reduced the migration and colony-forming abilities of blasts and leukemic-initiating cells (LICs) in both primary and relapsed AML. Thus, our study suggested that FEV maintains the homing and expansion of AML cells by activating ITGA4 transcription and that targeting ITGA4 inhibits the colony-forming and migration capacities of blasts and LICs. Thus, these findings suggested that the FEV-ITGA4 axis may be a therapeutic target for both primary and relapsed AML.https://www.frontiersin.org/articles/10.3389/fonc.2022.890346/fullFEVAML (acute myeloid leukemia)ITGA4homingexpansion |
| spellingShingle | Jubin Zhang Jubin Zhang Lijuan Qi Lijuan Qi Tanzhen Wang Tanzhen Wang Jingnan An Jingnan An Biqi Zhou Biqi Zhou Yanglan Fang Yanglan Fang Yujie Liu Yujie Liu Meng Shan Meng Shan Dengli Hong Depei Wu Depei Wu Yang Xu Yang Xu Tianhui Liu Tianhui Liu FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML Frontiers in Oncology FEV AML (acute myeloid leukemia) ITGA4 homing expansion |
| title | FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML |
| title_full | FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML |
| title_fullStr | FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML |
| title_full_unstemmed | FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML |
| title_short | FEV Maintains Homing and Expansion by Activating ITGA4 Transcription in Primary and Relapsed AML |
| title_sort | fev maintains homing and expansion by activating itga4 transcription in primary and relapsed aml |
| topic | FEV AML (acute myeloid leukemia) ITGA4 homing expansion |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.890346/full |
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