Identifying acute myeloid leukemia subtypes based on pathway enrichment
Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment st...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1557112/full |
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| author | Ling Zhong Ling Zhong Ling Zhong Ling Zhong Jiangti Luo Jiangti Luo Jiangti Luo Jiangti Luo Junze Dong Xiang Yang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang |
| author_facet | Ling Zhong Ling Zhong Ling Zhong Ling Zhong Jiangti Luo Jiangti Luo Jiangti Luo Jiangti Luo Junze Dong Xiang Yang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang |
| author_sort | Ling Zhong |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for AML by proposing a novel subtyping method. Through unsupervised clustering based on the enrichment scores of 14 pathways related to metabolism, immunity, DNA repair, and oncogenic signaling, we identified three AML subtypes: DNA repair (DR), immune-enriched (ImE), and immune-deprived (ImD), consistent in four independent datasets. DR is marked by high expression of DNA repair and metabolic pathways, high stemness and proliferation potential, as well as high sensitivity to chemotherapy. ImD is characterized by low expression of immune and oncogenic pathways, favorable survival prognosis, low mutation rates of RUNX1 and TP53, high homeostasis, and low migration potential. ImE exhibits high enrichment of immune and oncogenic pathways, low stemness and proliferation capacity, low homeostasis, high migration potential, and low sensitivity to chemotherapy. Our pathway enrichment-based subtyping approach would offer a promising framework for understanding the molecular heterogeneity of AML and guiding personalized treatment of this disease. |
| format | Article |
| id | doaj-art-129faa016c384bb3957f9c5770498e5e |
| institution | OA Journals |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-129faa016c384bb3957f9c5770498e5e2025-08-20T01:49:14ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15571121557112Identifying acute myeloid leukemia subtypes based on pathway enrichmentLing Zhong0Ling Zhong1Ling Zhong2Ling Zhong3Jiangti Luo4Jiangti Luo5Jiangti Luo6Jiangti Luo7Junze Dong8Xiang Yang9Xiaosheng Wang10Xiaosheng Wang11Xiaosheng Wang12Xiaosheng Wang13Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntelligent Pharmacy Interdisciplinary Research Center, China Pharmaceutical University, Nanjing, ChinaBig Data Research Institute, China Pharmaceutical University, Nanjing, ChinaInstitute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing, ChinaBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntelligent Pharmacy Interdisciplinary Research Center, China Pharmaceutical University, Nanjing, ChinaBig Data Research Institute, China Pharmaceutical University, Nanjing, ChinaInstitute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing, ChinaNanjing Foreign Language School, Nanjing, ChinaDepartment of Oncology, JunXie Hospital, Nanjing, ChinaBiomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, ChinaIntelligent Pharmacy Interdisciplinary Research Center, China Pharmaceutical University, Nanjing, ChinaBig Data Research Institute, China Pharmaceutical University, Nanjing, ChinaInstitute of Innovative Drug Discovery and Development, China Pharmaceutical University, Nanjing, ChinaAcute myeloid leukemia (AML) is the most common type of acute leukemia in adults and the second most common in children. Despite the introduction of targeted therapies, AML survival rates have shown limited improvement, particularly among older patients. This study explored personalized treatment strategies for AML by proposing a novel subtyping method. Through unsupervised clustering based on the enrichment scores of 14 pathways related to metabolism, immunity, DNA repair, and oncogenic signaling, we identified three AML subtypes: DNA repair (DR), immune-enriched (ImE), and immune-deprived (ImD), consistent in four independent datasets. DR is marked by high expression of DNA repair and metabolic pathways, high stemness and proliferation potential, as well as high sensitivity to chemotherapy. ImD is characterized by low expression of immune and oncogenic pathways, favorable survival prognosis, low mutation rates of RUNX1 and TP53, high homeostasis, and low migration potential. ImE exhibits high enrichment of immune and oncogenic pathways, low stemness and proliferation capacity, low homeostasis, high migration potential, and low sensitivity to chemotherapy. Our pathway enrichment-based subtyping approach would offer a promising framework for understanding the molecular heterogeneity of AML and guiding personalized treatment of this disease.https://www.frontiersin.org/articles/10.3389/fphar.2025.1557112/fullAMLacute myeloid leukemiapathway enrichment analysistranscriptome (RNA-seq)drug sensitivitysubtype |
| spellingShingle | Ling Zhong Ling Zhong Ling Zhong Ling Zhong Jiangti Luo Jiangti Luo Jiangti Luo Jiangti Luo Junze Dong Xiang Yang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang Xiaosheng Wang Identifying acute myeloid leukemia subtypes based on pathway enrichment Frontiers in Pharmacology AML acute myeloid leukemia pathway enrichment analysis transcriptome (RNA-seq) drug sensitivity subtype |
| title | Identifying acute myeloid leukemia subtypes based on pathway enrichment |
| title_full | Identifying acute myeloid leukemia subtypes based on pathway enrichment |
| title_fullStr | Identifying acute myeloid leukemia subtypes based on pathway enrichment |
| title_full_unstemmed | Identifying acute myeloid leukemia subtypes based on pathway enrichment |
| title_short | Identifying acute myeloid leukemia subtypes based on pathway enrichment |
| title_sort | identifying acute myeloid leukemia subtypes based on pathway enrichment |
| topic | AML acute myeloid leukemia pathway enrichment analysis transcriptome (RNA-seq) drug sensitivity subtype |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1557112/full |
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