The role of METTL14 in the progression of chronic myeloid leukemia
Objectives Chronic myeloid leukemia (CML), a clonal malignant disease arising from the BCR-ABL fusion gene, presents significant therapeutic challenges, particularly in chemotherapy resistance. The role of METTL14, a key m6A methyltransferase, is implicated in cancer biology, but its role in CML rem...
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| Language: | English |
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Taylor & Francis Group
2025-12-01
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| Series: | Hematology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/16078454.2025.2535819 |
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| author | Jing Zhang Zhi-Hua Liao Yan-Mei Xu Shu-Qi Li Fang-Min Zhong Ling Zhang Fang-Yi Yao Qin Bai Li-Hua Yao Bo Huang Jing Liu Xiao-Zhong Wang |
| author_facet | Jing Zhang Zhi-Hua Liao Yan-Mei Xu Shu-Qi Li Fang-Min Zhong Ling Zhang Fang-Yi Yao Qin Bai Li-Hua Yao Bo Huang Jing Liu Xiao-Zhong Wang |
| author_sort | Jing Zhang |
| collection | DOAJ |
| description | Objectives Chronic myeloid leukemia (CML), a clonal malignant disease arising from the BCR-ABL fusion gene, presents significant therapeutic challenges, particularly in chemotherapy resistance. The role of METTL14, a key m6A methyltransferase, is implicated in cancer biology, but its role in CML remains unclear.Methods Peripheral blood mononuclear cells (PBMCs) and CML cell lines (K562 and K562/G01) were conducted in vitro studies. mRNA levels were quantified by quantitative PCR (qPCR), and protein expressions were assessed by Western Blotting. Cell viability and apoptosis were measured using the CCK-8 and flow cytometry, respectively. Drug resistance was evaluated by determining the half-maximal inhibitory concentration (IC50). m6A levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and modification sites were predicted by SRAMP and confirmed with a SELECT detection assay. Gene interactions were validated through luciferase assays.Results METTL14 expression was significantly elevated in imatinib-resistant CML patients (P=0.005) and K562/G01 cells (P=0.01), correlating with increased m6A modification levels (P=0.032). Overexpression of METTL14 enhanced m6A methylation, promoted cell proliferation, inhibited apoptosis, and increased imatinib resistance in CML cells. Conversely, METTL14 silencing reduced m6A levels, induced G0/G1 arrest, and enhanced apoptosis (P=0.01). Mechanistically, the luciferase assay results demonstrated that METTL14-mediated m6A modification at the A1001 site of Bcl-x mRNA facilitated HNRNPC-dependent splicing. Consequently, this modification results in shifting Bcl-xS to Bcl-xL and inactivating the BCL-2/BAX/Caspase-3 pathway.Conclusion METTL14-driven m6A modification regulates the splicing pattern of Bcl-x, and may facilitate the progression of CML. Keywords: CML, METTL14, N6-methyladenine, Bcl-x, Alternative splicing, resistance, imatinib, progression. |
| format | Article |
| id | doaj-art-c406a9e0b65d4fd1bd7a3c612ea35766 |
| institution | DOAJ |
| issn | 1607-8454 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Hematology |
| spelling | doaj-art-c406a9e0b65d4fd1bd7a3c612ea357662025-08-20T03:23:33ZengTaylor & Francis GroupHematology1607-84542025-12-0130110.1080/16078454.2025.2535819The role of METTL14 in the progression of chronic myeloid leukemiaJing Zhang0Zhi-Hua Liao1Yan-Mei Xu2Shu-Qi Li3Fang-Min Zhong4Ling Zhang5Fang-Yi Yao6Qin Bai7Li-Hua Yao8Bo Huang9Jing Liu10Xiao-Zhong Wang11Jiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaDepartment of Clinical Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaKey Laboratory of Laboratory Medical Diagnostics, Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaJiangxi Province Key Laboratory of Immunology and Inflammation, Jiangxi Provincial Clinical Research Center for Laboratory Medicine, Department of Clinical Laboratory, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, People’s Republic of ChinaObjectives Chronic myeloid leukemia (CML), a clonal malignant disease arising from the BCR-ABL fusion gene, presents significant therapeutic challenges, particularly in chemotherapy resistance. The role of METTL14, a key m6A methyltransferase, is implicated in cancer biology, but its role in CML remains unclear.Methods Peripheral blood mononuclear cells (PBMCs) and CML cell lines (K562 and K562/G01) were conducted in vitro studies. mRNA levels were quantified by quantitative PCR (qPCR), and protein expressions were assessed by Western Blotting. Cell viability and apoptosis were measured using the CCK-8 and flow cytometry, respectively. Drug resistance was evaluated by determining the half-maximal inhibitory concentration (IC50). m6A levels were quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS), and modification sites were predicted by SRAMP and confirmed with a SELECT detection assay. Gene interactions were validated through luciferase assays.Results METTL14 expression was significantly elevated in imatinib-resistant CML patients (P=0.005) and K562/G01 cells (P=0.01), correlating with increased m6A modification levels (P=0.032). Overexpression of METTL14 enhanced m6A methylation, promoted cell proliferation, inhibited apoptosis, and increased imatinib resistance in CML cells. Conversely, METTL14 silencing reduced m6A levels, induced G0/G1 arrest, and enhanced apoptosis (P=0.01). Mechanistically, the luciferase assay results demonstrated that METTL14-mediated m6A modification at the A1001 site of Bcl-x mRNA facilitated HNRNPC-dependent splicing. Consequently, this modification results in shifting Bcl-xS to Bcl-xL and inactivating the BCL-2/BAX/Caspase-3 pathway.Conclusion METTL14-driven m6A modification regulates the splicing pattern of Bcl-x, and may facilitate the progression of CML. Keywords: CML, METTL14, N6-methyladenine, Bcl-x, Alternative splicing, resistance, imatinib, progression.https://www.tandfonline.com/doi/10.1080/16078454.2025.2535819CMLMETTL14N6-methyladenineBcl-xAlternative splicingresistance |
| spellingShingle | Jing Zhang Zhi-Hua Liao Yan-Mei Xu Shu-Qi Li Fang-Min Zhong Ling Zhang Fang-Yi Yao Qin Bai Li-Hua Yao Bo Huang Jing Liu Xiao-Zhong Wang The role of METTL14 in the progression of chronic myeloid leukemia Hematology CML METTL14 N6-methyladenine Bcl-x Alternative splicing resistance |
| title | The role of METTL14 in the progression of chronic myeloid leukemia |
| title_full | The role of METTL14 in the progression of chronic myeloid leukemia |
| title_fullStr | The role of METTL14 in the progression of chronic myeloid leukemia |
| title_full_unstemmed | The role of METTL14 in the progression of chronic myeloid leukemia |
| title_short | The role of METTL14 in the progression of chronic myeloid leukemia |
| title_sort | role of mettl14 in the progression of chronic myeloid leukemia |
| topic | CML METTL14 N6-methyladenine Bcl-x Alternative splicing resistance |
| url | https://www.tandfonline.com/doi/10.1080/16078454.2025.2535819 |
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