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

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 24; pp. e70306 - n/a
• Main Authors: Chen, Chung‐Hsing, Chen, Tsung‐Chih, Wu, Ting‐Shuan, Hsiao, Tzu‐Hung, Chen, Jo‐Mei Maureen, Huang, Chi‐Ying F., Cheng, Po‐Liang, Tsai, Jia‐Rung, Teng, Chieh‐Lin Jerry
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2024; John Wiley and Sons Inc
• Subjects: Acute myeloid leukemia; Adult; Aged; AML; Biomarkers; Biomarkers, Tumor - metabolism; Bone marrow; Chemoresistance; chemosensitivity; Chemotherapy; Cytogenetics; Datasets; Dendritic cells; Drug Resistance, Neoplasm; Female; Genes; Genomes; Genomics; Hemopoiesis; Humans; Induction therapy; leukaemic stem cells; Leukemia; Leukemia, Myeloid, Acute - drug therapy; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Leukocytes (mononuclear); Male; Medical prognosis; Middle Aged; MPO; Neoplastic Stem Cells - drug effects; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Original; Peroxidase; Peroxidase - metabolism; Phosphorylation; Prognosis; Prospective Studies; Stem cells; Thyroid-stimulating hormone; Transforming growth factor-a; TRH; United States > US; AML; TRH; leukaemic stem cells; chemosensitivity; MPO
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70306

ABSTRACT 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) (log2 fold‐change = 0.89; adjusted p < 0.0001) and thyrotropin‐releasing hormone (TRH) (log2 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.