Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia
BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we e...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1302356/full |
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| author | Peng Ke Peng Ke Jundan Xie Jundan Xie Ting Xu Ting Xu Meiyu Chen Meiyu Chen Yusha Guo Yusha Guo Ying Wang Ying Wang Huiying Qiu Huiying Qiu Depei Wu Depei Wu Zhao Zeng Zhao Zeng Suning Chen Suning Chen Xiebing Bao Xiebing Bao |
| author_facet | Peng Ke Peng Ke Jundan Xie Jundan Xie Ting Xu Ting Xu Meiyu Chen Meiyu Chen Yusha Guo Yusha Guo Ying Wang Ying Wang Huiying Qiu Huiying Qiu Depei Wu Depei Wu Zhao Zeng Zhao Zeng Suning Chen Suning Chen Xiebing Bao Xiebing Bao |
| author_sort | Peng Ke |
| collection | DOAJ |
| description | BackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis. |
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| format | Article |
| id | doaj.art-c6ce763ab9a84e0f871224f0e948d099 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-09T14:00:20Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-c6ce763ab9a84e0f871224f0e948d0992023-11-30T08:43:24ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-11-011310.3389/fonc.2023.13023561302356Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemiaPeng Ke0Peng Ke1Jundan Xie2Jundan Xie3Ting Xu4Ting Xu5Meiyu Chen6Meiyu Chen7Yusha Guo8Yusha Guo9Ying Wang10Ying Wang11Huiying Qiu12Huiying Qiu13Depei Wu14Depei Wu15Zhao Zeng16Zhao Zeng17Suning Chen18Suning Chen19Xiebing Bao20Xiebing Bao21National 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, 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, ChinaBackgroundSatisfactory responses can be obtained for acute myeloid leukemia (AML) treated by Venetoclax (VEN)-based therapy. However, there are still quite a few AML patients (AMLs) resistant to VEN, and it is critical to understand whether VEN-resistance is regulated by senescence.MethodsHere, we established and validated a signature for predicting AML prognosis based on VEN resistance-related senescence genes (VRSGs). In this study, 51 senescence genes were identified with VEN-resistance in AML. Using LASSO algorithms and multiple AML cohorts, a VEN-resistance senescence prognostic model (VRSP-M) was developed and validated based on 6-senescence genes.ResultsAccording to the median score of the signature, AMLs were classified into two subtypes. A worse prognosis and more adverse features occurred in the high-risk subtype, including older patients, non-de novo AML, poor cytogenetics, adverse risk of European LeukemiaNet (ELN) 2017 recommendation, and TP53 mutation. Patients in the high-risk subtype were mainly involved in monocyte differentiation, senescence, NADPH oxidases, and PD1 signaling pathway. The model’s risk score was significantly associated with VEN-resistance, immune features, and immunotherapy response in AML. In vitro, the IC50 values of ABT-199 (VEN) rose progressively with increasing expression of G6PD and BAG3 in AML cell lines.ConclusionsThe 6-senescence genes prognostic model has significant meaning for the prediction of VEN-resistance, guiding personalized molecularly targeted therapies, and improving AML prognosis.https://www.frontiersin.org/articles/10.3389/fonc.2023.1302356/fullvenetoclax resistancesenescenceprognosisacute myeloid leukemiaimmunotherapy |
| spellingShingle | Peng Ke Peng Ke Jundan Xie Jundan Xie Ting Xu Ting Xu Meiyu Chen Meiyu Chen Yusha Guo Yusha Guo Ying Wang Ying Wang Huiying Qiu Huiying Qiu Depei Wu Depei Wu Zhao Zeng Zhao Zeng Suning Chen Suning Chen Xiebing Bao Xiebing Bao Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia Frontiers in Oncology venetoclax resistance senescence prognosis acute myeloid leukemia immunotherapy |
| title | Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia |
| title_full | Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia |
| title_fullStr | Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia |
| title_full_unstemmed | Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia |
| title_short | Identification of a venetoclax-resistance prognostic signature base on 6-senescence genes and its clinical significance for acute myeloid leukemia |
| title_sort | identification of a venetoclax resistance prognostic signature base on 6 senescence genes and its clinical significance for acute myeloid leukemia |
| topic | venetoclax resistance senescence prognosis acute myeloid leukemia immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1302356/full |
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