Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia
IntroductionAcute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-...
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Frontiers Media S.A.
2023-10-01
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1281687/full |
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| author | Zhongzheng Li Xin Liu Lan Wang Huabin Zhao Shenghui Wang Guoying Yu Depei Wu Jianhong Chu Jingjing Han |
| author_facet | Zhongzheng Li Xin Liu Lan Wang Huabin Zhao Shenghui Wang Guoying Yu Depei Wu Jianhong Chu Jingjing Han |
| author_sort | Zhongzheng Li |
| collection | DOAJ |
| description | IntroductionAcute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m6A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance.MethodsTo investigate the m6A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m6A modification activity of cells in AML patients based on 23 m6A modification enzymes and further integrated with bulk RNA-seq data.ResultsWe found that m6A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m6A modification status in leukemia cells, while active m6A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m6A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by RUNX1 mutation and KMT2A copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of IGF2BP3 and FMR1, and low expression level of ELAVL1 and YTHDF2. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy.DiscussionCollectively, our findings suggest that m6A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy. |
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| last_indexed | 2024-03-11T14:29:14Z |
| publishDate | 2023-10-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-77a636f2a0614c4ea2c686a737380f332023-10-31T11:12:55ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12816871281687Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemiaZhongzheng Li0Xin Liu1Lan Wang2Huabin Zhao3Shenghui Wang4Guoying Yu5Depei Wu6Jianhong Chu7Jingjing Han8State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaState Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, ChinaState Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, ChinaState Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, ChinaState Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Pulmonary Fibrosis, College of Life Science, Institute of Biomedical Science, Henan Normal University, Xinxiang, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaInstitute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaThe First Affiliated Hospital of Soochow University, National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, ChinaIntroductionAcute myeloid leukemia (AML) is a type of blood cancer that is identified by the unrestricted growth of immature myeloid cells within the bone marrow. Despite therapeutic advances, AML prognosis remains highly variable, and there is a lack of biomarkers for customizing treatment. RNA N6-methyladenosine (m6A) modification is a reversible and dynamic process that plays a critical role in cancer progression and drug resistance.MethodsTo investigate the m6A modification patterns in AML and their potential clinical significance, we used the AUCell method to describe the m6A modification activity of cells in AML patients based on 23 m6A modification enzymes and further integrated with bulk RNA-seq data.ResultsWe found that m6A modification was more effective in leukemic cells than in immune cells and induced significant changes in gene expression in leukemic cells rather than immune cells. Furthermore, network analysis revealed a correlation between transcription factor activation and the m6A modification status in leukemia cells, while active m6A-modified immune cells exhibited a higher interaction density in their gene regulatory networks. Hierarchical clustering based on m6A-related genes identified three distinct AML subtypes. The immune dysregulation subtype, characterized by RUNX1 mutation and KMT2A copy number variation, was associated with a worse prognosis and exhibited a specific gene expression pattern with high expression level of IGF2BP3 and FMR1, and low expression level of ELAVL1 and YTHDF2. Notably, patients with the immune dysregulation subtype were sensitive to immunotherapy and chemotherapy.DiscussionCollectively, our findings suggest that m6A modification could be a potential therapeutic target for AML, and the identified subtypes could guide personalized therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1281687/fullacute myeloid leukemiaN6-methyladenosine modificationsubtypesingle-cell transcriptometumor microenvironment |
| spellingShingle | Zhongzheng Li Xin Liu Lan Wang Huabin Zhao Shenghui Wang Guoying Yu Depei Wu Jianhong Chu Jingjing Han Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia Frontiers in Immunology acute myeloid leukemia N6-methyladenosine modification subtype single-cell transcriptome tumor microenvironment |
| title | Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| title_full | Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| title_fullStr | Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| title_full_unstemmed | Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| title_short | Integrated analysis of single-cell RNA-seq and bulk RNA-seq reveals RNA N6-methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| title_sort | integrated analysis of single cell rna seq and bulk rna seq reveals rna n6 methyladenosine modification associated with prognosis and drug resistance in acute myeloid leukemia |
| topic | acute myeloid leukemia N6-methyladenosine modification subtype single-cell transcriptome tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1281687/full |
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