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

Medientyp: E-Book; Sonderdruck

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

Beteiligte: Kreutmair, Stefanie [Verfasser:in]; Klingeberg, Cathrin [Verfasser:in]; Poggio, Teresa [Verfasser:in]; Geoffroy, Andrieux [Verfasser:in]; Keller, Alexander [Verfasser:in]; Miething, Cornelius [Verfasser:in]; Follo, Marie [Verfasser:in]; Pfeifer, Dietmar [Verfasser:in]; Shoumariyeh, Khalid [Verfasser:in]; Lengerke, Claudia [Verfasser:in]; Gonzalez Menendez, Irene [Verfasser:in]; Fend, Falko [Verfasser:in]; Zeiser, Robert [Verfasser:in]; Turner, Suzanne D. [Verfasser:in]; Quintanilla-Martinez, Leticia [Verfasser:in]; Börries, Melanie [Verfasser:in]; Duyster, Justus [Verfasser:in]; Illert, Anna Lena [Verfasser:in]

Erschienen: London: Springer Nature, 2020

Umfang: 1 Online-Ressource (14 Seiten); Diagramme; Supplementary information

Sprache: Englisch

DOI: 10.1038/s41375-020-0789-x

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Beschreibung: 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

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