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
Department of Mathematics, University of Taipei, Taipei, Taiwan.
National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan.
J Cell Mol Med. 2024 Dec;28(24):e70306. doi: 10.1111/jcmm.70306.
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 fold-change = 0.89; adjusted p < 0.0001) and thyrotropin-releasing hormone (TRH) (log 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.
白血病干细胞（LSCs）是急性髓系白血病（AML）化疗耐药的主要原因。识别LSCs中能够预测AML化疗敏感性的潜在生物标志物是关键。这项前瞻性研究纳入了20例连续的初发AML患者，这些患者接受了“7+3”诱导治疗。患者被分为完全缓解（CR，n=15）组和未完全缓解（非CR，n=5）组。我们使用单细胞RNA测序技术，检测了AML患者诊断时骨髓单个核细胞的细胞状态，并在这些细胞中鉴定出LSCs。我们的结果显示，在非CR的AML患者中，观察到AML细胞群体中造血过程中未成熟细胞比例显著增加。此外，CR组LSCs中髓过氧化物酶（MPO）（对数变化倍数=0.89；校正p<0.0001）和促甲状腺激素释放激素（TRH）（对数变化倍数=0.65；校正p<0.0001）的表达高于非CR组。此外，MPO和TRH表达较高的患者无复发生存期改善（MPO，p=0.002；TRH，p=0.009）和总生存期改善（MPO，p=0.002；TRH，p<0.001）。MPO或TRH与化疗敏感性之间的联系可能与转化生长因子的下调和干扰素-α的上调有关。总之，LSCs中的MPO和TRH可作为AML化疗敏感性的生物标志物。
