Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model
| Autor: | Kreutmair, Stefanie, Klingeberg, Cathrin, Poggio, Teresa, Andrieux, Geoffroy, Keller, Alexander, Miething, Cornelius, Follo, Marie, Pfeifer, Dietmar, Shoumariyeh, Khalid, Lengerke, Claudia, Gonzalez-Menendez, Irene, Fend, Falko, Zeiser, Robert, Turner, Suzanne D., Quintanilla-Martinez, Leticia, Boerries, Melanie, Duyster, Justus, Illert, Anna L. |
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| Popis: | Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN Alkatras Funder: DFG (CRC850) Funder: DFG (CRC850) BMBF (DeCaRe, FKZ 01ZX1409B) Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN Alkatras DFG (FOR 2033 B1) Funder: DJCLS (R14/22) MSCA-ITN-2015-ETN Alkatras Grant from the Government of Baden-Württemberg (BSL) While cancer stem cells are well established in certain hematologic and solid malignancies, their existence in T cell lymphoma is unclear and the origin of disease is not fully understood. To examine the existence of lymphoma stem cells, we utilized a mouse model of anaplastic large cell lymphoma. Established NPM-ALK+ lymphomas contained heterogeneous cell populations ranging from mature T cells to undifferentiated hematopoietic stem cells. Interestingly, CD4−/CD8− double negative (DN) lymphoma cells aberrantly expressed the T cell receptor α/β chain. Serial transplantation of sorted CD4/CD8 and DN lymphoma subpopulations identified lymphoma stem cells within the DN3/DN4 T cell population, whereas all other subpopulations failed to establish serial lymphomas. Moreover, transplanted lymphoma DN3/DN4 T cells were able to differentiate and gave rise to mature lymphoma T cells. Gene expression analyses unmasked stem-cell-like transcriptional regulation of the identified lymphoma stem cell population. Furthermore, these lymphoma stem cells are characterized by low CD30 expression levels, which might contribute to limited long-term therapeutic success in patients treated with anti-CD30-targeted therapies. In summary, our results highlight the existence of a lymphoma stem cell population in a NPM-ALK-driven CD30+ mouse model, thereby giving the opportunity to test innovative treatment strategies developed to eradicate the origin of disease. |
| Databáze: | OpenAIRE |
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