Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells

SIMPLE SUMMARY: Cancer treatments usually gain good responses; however, some tumors relapse frequently. Acute Myeloid Leukemia (AML) is notorious for its robust relapse. This is attributed to the leukemic stem cells (LSCs). We used a murine syngeneic leukemia model, ML23, to identify and study LSCs in syngeneic settings. Hereby, we present the prospective isolation of a defined LSC sub-population, encompassing the potency to pass disease from mouse to mouse. We further provide molecular insights and whole transcriptome analysis. Importantly, the ML23 LSC sub-population expresses therapeutic targeted genes and provides a model for research in immune-competent animals. ABSTRACT: 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 cKit(+)CD9(−)CD48(+)Mac1(−/low), 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.