Hydroxy-wybutosine tRNA modifications as indicators of disease progression and therapeutic targets in leukaemia
This article relates to:
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Targeting RNA modifications in leukaemia: Epitranscriptomic drugs are the new kids on the block
- Volume 206Issue 2British Journal of Haematology
- pages: 785-787
- First Published online: November 10, 2024
Xu Chen
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China
Search for more papers by this authorRui-Ze Gong
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorLiu-Ying Mo
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYa-Ting Cheng
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYu Ma
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYi-Tao Qi
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China
Search for more papers by this authorTong-Meng Yan
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorCorresponding Author
Zhi-Hong Jiang
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Correspondence
Zhi-Hong Jiang, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau SAR, China.
Email: [email protected]
Search for more papers by this authorXu Chen
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China
Search for more papers by this authorRui-Ze Gong
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorLiu-Ying Mo
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYa-Ting Cheng
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYu Ma
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorYi-Tao Qi
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi, China
Search for more papers by this authorTong-Meng Yan
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Search for more papers by this authorCorresponding Author
Zhi-Hong Jiang
State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau SAR, China
Correspondence
Zhi-Hong Jiang, State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau SAR, China.
Email: [email protected]
Search for more papers by this authorXu Chen and Rui-Ze Gong contributed equally to this work.
[Correction added on 14 February 2025, after first online publication: The subcategory has been changed.]
Summary
Therapeutic approaches for acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS) differ due to distinct diagnostic criteria and treatment strengths. However, reliable biomarkers to differentiate AML from MDS are needed. This study investigated transfer RNA (tRNA) modifications, particularly hydroxy-wybutosine (OHyW), in the transition from MDS to AML. We found a significant decrease in OHyW and its biosynthetic enzyme leucine carboxyl methyltransferase 2 (LCMT2, alias symbol is TYW4) levels in AML compared to MDS. Mass spectrometric analysis revealed distinct tRNA modification patterns, with AML showing decreased OHyW and increased precursor levels, indicating a disrupted biosynthetic pathway. Lower LCMT2 expression correlated with reduced drug sensitivity and limited differentiation potential in AML cell lines. The results highlight the pivotal role of tRNA modifications in the progression from MDS to AML and suggest that targeting LCMT2 may enhance therapeutic outcomes in AML. By understanding these molecular mechanisms, we can develop new diagnostic markers and therapeutic strategies, potentially transforming the clinical management of AML and improving patient outcomes.
CONFLICT OF INTEREST STATEMENT
The authors state that they have no known financial conflicts of interest or personal relationships that could have influenced the work reported in this paper.
Open Research
DATA AVAILABILITY STATEMENT
Upon reasonable request, the data supporting the findings of this study are available from the corresponding author.
Supporting Information
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| bjh19873-sup-0001-FigureS1.tifTIFF image, 25.8 MB |
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| bjh19873-sup-0002-FigureS2.tifTIFF image, 24.7 MB |
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| bjh19873-sup-0003-Supinfo.docxWord 2007 document , 17.6 KB |
Data S1. |
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