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Existence of reprogrammed lymphoma stem cells in a murine ALCL-like model.

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Kreutmair, Stefanie 
Klingeberg, Cathrin 
Poggio, Teresa 
Andrieux, Geoffroy 
Keller, Alexander 


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.


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)


Anaplastic Lymphoma Kinase, Animals, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Line, Disease Models, Animal, Female, Gene Expression, Ki-1 Antigen, Lymphoma, Large-Cell, Anaplastic, Lymphoma, T-Cell, Male, Mice, Mice, Inbred C57BL, NIH 3T3 Cells, Stem Cells, Translocation, Genetic

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Springer Science and Business Media LLC
European Commission Horizon 2020 (H2020) Marie Sk?odowska-Curie actions (675712)