HOPX as a tumour-suppressive protein in T-cell acute lymphoblastic leukaemia
Corresponding Author
Chien-Chin Lin
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
Correspondence
Chien-Chin Lin and Wen-Chien Chou, Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Email: [email protected] and [email protected]
Search for more papers by this authorChia-Lang Hsu
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorChi-Yuan Yao
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorYu-Hung Wang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorChang-Tsu Yuan
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Department of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan
Search for more papers by this authorYuan-Yeh Kuo
Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorJhih-Yi Lee
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorPin-Tsen Shih
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorChein-Jun Kao
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorPo-Han Chuang
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorYueh-Chwen Hsu
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorHsin-An Hou
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Wen-Chien Chou
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Correspondence
Chien-Chin Lin and Wen-Chien Chou, Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Email: [email protected] and [email protected]
Search for more papers by this authorHwei-Fang Tien
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology and Medical Oncology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Chien-Chin Lin
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan
Correspondence
Chien-Chin Lin and Wen-Chien Chou, Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Email: [email protected] and [email protected]
Search for more papers by this authorChia-Lang Hsu
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorChi-Yuan Yao
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorYu-Hung Wang
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorChang-Tsu Yuan
Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
Department of Pathology, National Taiwan University Cancer Center, Taipei, Taiwan
Search for more papers by this authorYuan-Yeh Kuo
Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
Search for more papers by this authorJhih-Yi Lee
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorPin-Tsen Shih
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorChein-Jun Kao
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorPo-Han Chuang
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorYueh-Chwen Hsu
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorHsin-An Hou
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Search for more papers by this authorCorresponding Author
Wen-Chien Chou
Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Correspondence
Chien-Chin Lin and Wen-Chien Chou, Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd., Taipei 10002, Taiwan.
Email: [email protected] and [email protected]
Search for more papers by this authorHwei-Fang Tien
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
Division of Hematology and Medical Oncology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan
Search for more papers by this author[Correction added on 14 February 2025, after first online publication: The subcategory has been changed.]
Summary
The homeodomain protein homeobox (HOPX), a multifaceted regulator of cellular functions and developmental processes, is predominantly expressed in stem cells across diverse tissues; it has also emerged as a tumour suppressor in various solid cancers. However, its role in haematological malignancies still remains undefined. This study aimed to elucidate its significance in T-cell acute lymphoblastic leukaemia (T-ALL). We firstly uncovered a novel link between reduced HOPX expression, its promoter hypermethylation and increased tumour burden in patients with T-ALL, suggesting its tumour-suppressive role. Next, we induced T-ALL by transducing intracellular NOTCH1 (ICN1) into mice with either conditional knock-in at the Rosa26 locus or knockout of Hopx. We found that T-ALL development was markedly accelerated and impeded in backgrounds with low and high Hopx expression respectively. Further analysis revealed Hopx's roles in modulating the Wnt-β-catenin pathway, a pivotal regulator of the downstream Myc signalling involved in T-ALL transformation and progression.
Graphical Abstract
We firstly uncovered a novel link between reduced HOPX expression, its promoter hypermethylation and increased tumour burden in patients with T-ALL, suggesting its tumour-suppressive role. Next, we induced T-ALL by transducing intracellular NOTCH1 (ICN1) into mice with either conditional knock-in at the Rosa26 locus or knockout of Hopx. We found that T-ALL development was markedly accelerated and impeded in backgrounds with low and high Hopx expression respectively. Further analysis revealed Hopx's roles in modulating the Wnt-β-catenin pathway, a pivotal regulator of the downstream Myc signalling involved in T-ALL transformation and progression.
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon request.
Supporting Information
| Filename | Description |
|---|---|
| bjh19965-sup-0001-DataS1.docxWord 2007 document , 21.8 MB |
Data S1. |
| bjh19965-sup-0002-TableS1-S5.xlsxExcel 2007 spreadsheet , 112.4 KB |
Tables S1–S5. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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