Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model
| Autor: | Stefanie Kreutmair, Marie Follo, Leticia Quintanilla-Martinez, Irene Gonzalez-Menendez, Dietmar Pfeifer, Melanie Boerries, Khalid Shoumariyeh, Cathrin Klingeberg, Justus Duyster, Cornelius Miething, Alexander Keller, Teresa Poggio, Suzanne D. Turner, Geoffroy Andrieux, Robert Zeiser, Falko Fend, Anna Lena Illert, Claudia Lengerke |
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| Přispěvatelé: | Miething, Cornelius [0000-0003-4699-3805], Lengerke, Claudia [0000-0001-5442-2805], Fend, Falko [0000-0002-5496-293X], Turner, Suzanne D. [0000-0002-8439-4507], Boerries, Melanie [0000-0002-3670-0602], Apollo - University of Cambridge Repository, Turner, Suzanne D [0000-0002-8439-4507] |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
CD4-Positive T-Lymphocytes Male Cancer Research CD30 45/44 Gene Expression CD8-Positive T-Lymphocytes Translocation Genetic 42/100 Mice 0302 clinical medicine immune system diseases hemic and lymphatic diseases 631/67/395 T-cell lymphoma Anaplastic Lymphoma Kinase Anaplastic large-cell lymphoma Stem Cells Hematology 3. Good health 13/31 Haematopoiesis Oncology 030220 oncology & carcinogenesis Lymphoma Large-Cell Anaplastic 64/60 Female Stem cell 631/67/70 631/67/71 Ki-1 Antigen 13/109 Biology 631/67/1990/291/1621/1916 Lymphoma T-Cell Article Cell Line 03 medical and health sciences Cancer stem cell medicine Animals 64/110 medicine.disease 38/61 Lymphoma Mice Inbred C57BL Disease Models Animal 030104 developmental biology Cancer research NIH 3T3 Cells CD8 |
| Zdroj: | Leukemia |
| ISSN: | 1476-5551 |
| Popis: | 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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