Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells
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 hum...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-01-01
|
| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/3/720 |
| _version_ | 1797625050050854912 |
|---|---|
| author | Michael Chamo Omri Koren Oron Goldstein Nir Bujanover Nurit Keinan Ye’ela Scharff Roi Gazit |
| author_facet | Michael Chamo Omri Koren Oron Goldstein Nir Bujanover Nurit Keinan Ye’ela Scharff Roi Gazit |
| author_sort | Michael Chamo |
| collection | DOAJ |
| description | 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<sup>+</sup>CD9<sup>−</sup>CD48<sup>+</sup>Mac1<sup>−/low</sup>, 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. |
| first_indexed | 2024-03-11T09:51:20Z |
| format | Article |
| id | doaj.art-af7cb3ce826f4f5da3945e817349591c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:51:20Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-af7cb3ce826f4f5da3945e817349591c2023-11-16T16:16:14ZengMDPI AGCancers2072-66942023-01-0115372010.3390/cancers15030720Molecular Mechanisms in Murine Syngeneic Leukemia Stem CellsMichael Chamo0Omri Koren1Oron Goldstein2Nir Bujanover3Nurit Keinan4Ye’ela Scharff5Roi Gazit6The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelThe Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Science, Ben-Gurion University of the Negev, Beer Shevap 8410501, IsraelAcute 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<sup>+</sup>CD9<sup>−</sup>CD48<sup>+</sup>Mac1<sup>−/low</sup>, 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.https://www.mdpi.com/2072-6694/15/3/720syngeneic modelAMLleukemic stem cell |
| spellingShingle | Michael Chamo Omri Koren Oron Goldstein Nir Bujanover Nurit Keinan Ye’ela Scharff Roi Gazit Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells Cancers syngeneic model AML leukemic stem cell |
| title | Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells |
| title_full | Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells |
| title_fullStr | Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells |
| title_full_unstemmed | Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells |
| title_short | Molecular Mechanisms in Murine Syngeneic Leukemia Stem Cells |
| title_sort | molecular mechanisms in murine syngeneic leukemia stem cells |
| topic | syngeneic model AML leukemic stem cell |
| url | https://www.mdpi.com/2072-6694/15/3/720 |
| work_keys_str_mv | AT michaelchamo molecularmechanismsinmurinesyngeneicleukemiastemcells AT omrikoren molecularmechanismsinmurinesyngeneicleukemiastemcells AT orongoldstein molecularmechanismsinmurinesyngeneicleukemiastemcells AT nirbujanover molecularmechanismsinmurinesyngeneicleukemiastemcells AT nuritkeinan molecularmechanismsinmurinesyngeneicleukemiastemcells AT yeelascharff molecularmechanismsinmurinesyngeneicleukemiastemcells AT roigazit molecularmechanismsinmurinesyngeneicleukemiastemcells |