1. Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model
- Author
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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, 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, and Turner, Suzanne D [0000-0002-8439-4507]
- Subjects
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 - Abstract
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.
- Published
- 2019