Myeloperoxidase and Thyrotropin-Releasing Hormone Within Leukaemia Stem Cells Increased Chemosensitivity in Acute Myeloid Leukaemia.

Autor: Chen CH; Department of Mathematics, University of Taipei, Taipei, Taiwan.; National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan., Chen TC; Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan., Wu TS; Department of Biomedical Sciences, Chung Shan Medical University, Taichung, Taiwan.; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan., Hsiao TH; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of Public Health, Fu Jen Catholic University, New Taipei City, Taiwan.; Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan., Chen JM; Department of Applied Chemistry, National Chi Nan University, Puli, Nantou, Taiwan., Huang CF; Institute of Biopharmaceutical Sciences, National Yang-Ming Chiao Tung University, Taipei, Taiwan., Cheng PL; Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Tsai JR; Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan., Teng CJ; Division of Hematology/Medical Oncology, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.; Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.; School of Medicine, Chung Shan Medical University, Taichung, Taiwan.; Department of Life Science, Tunghai University, Taichung, Taiwan.; Program in Translational Medicine, National Chung Hsing University, Taichung, Taiwan.; Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan.
Jazyk: angličtina
Zdroj: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Dec; Vol. 28 (24), pp. e70306.
DOI: 10.1111/jcmm.70306
Abstrakt: Leukaemia stem cells (LSCs) are major contributors to chemoresistance in acute myeloid leukaemia (AML). Identifying potential biomarkers within LSCs that can predict chemosensitivity in AML is key. This prospective study involved 20 consecutive de novo AML patients who underwent '7 + 3' induction therapy. The patients were divided into CR (n = 15) and non-CR (n = 5) groups. Using single-cell RNA sequencing, we examined the cellular states of bone marrow mononuclear cells from AML patients at diagnosis and identified LSC among these cells. Our results showed that in non-CR AML patients, a significant increase in the proportion of immature cells during haematopoiesis within the AML cell populations was observed. Moreover, the expression of myeloperoxidase (MPO) (log 2 fold-change = 0.89; adjusted p < 0.0001) and thyrotropin-releasing hormone (TRH) (log 2 fold-change = 0.65; adjusted p < 0.0001) was higher within LSCs in the CR group than in the non-CR group. Furthermore, patients with higher expression of MPO and TRH demonstrated improved relapse-free survival (p = 0.002 for MPO; p = 0.009 for TRH) and overall survival (p = 0.002 for MPO; p < 0.001 for TRH). The connection between MPO or TRH and chemosensitivity could be linked with the downregulation of transforming growth factor and the upregulation of interferon-α. In conclusion, MPO and TRH in LSCs could serve as chemosensitivity biomarkers in AML.
(© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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