Chamo Michael, Koren Omri, Goldstein Oron, Bujanover Nir, Keinan Nurit, Scharff Ye'ela, Gazit Roi
The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, Israel.
Cancers (Basel). 2023 Jan 24;15(3):720. doi: 10.3390/cancers15030720.
Acute Myeloid Leukemia (AML) is a severe disease with a very high relapse rate. AML relapse may be attributable to leukemic stem cells (LSC). Notably, the "cancer stem cell" theory, which relates to LSCs, is controversial and criticized due to the technical peculiarities of the xenotransplant of human cells into mice. In this study, we searched for possible LSCs in an immunocompetent synergetic mice model. First, we found phenotypic heterogeneity in the ML23 leukemia line. We prospectively isolated a sub-population using the surface markers cKitCD9CD48Mac1, which have the potency to relapse the disease. Importantly, this sub-population can pass in syngeneic hosts and retrieve the heterogeneity of the parental ML23 leukemia line. The LSC sub-population resides in various organs. We present a unique gene expression signature of the LSC in the ML23 model compared to the other sub-populations. Interestingly, the ML23 LSC sub-population expresses therapeutic targeted genes such as CD47 and CD93. Taken together, we present the identification and molecular characterization of LSCs in a syngeneic murine model.
急性髓系白血病（AML）是一种复发率极高的严重疾病。AML复发可能归因于白血病干细胞（LSC）。值得注意的是，与LSCs相关的“癌症干细胞”理论因将人类细胞异种移植到小鼠体内的技术特性而存在争议并受到批评。在本研究中，我们在具有免疫活性的协同小鼠模型中寻找可能的LSCs。首先，我们在ML23白血病细胞系中发现了表型异质性。我们使用表面标志物cKitCD9CD48Mac1前瞻性地分离出一个亚群，该亚群具有使疾病复发的能力。重要的是，这个亚群可以在同基因宿主中传代并恢复亲本ML23白血病细胞系的异质性。LSC亚群存在于各个器官中。与其他亚群相比，我们展示了ML23模型中LSC独特的基因表达特征。有趣的是，ML23 LSC亚群表达治疗靶点基因，如CD47和CD93。综上所述，我们展示了同基因小鼠模型中LSCs的鉴定和分子特征。
