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

Leukemia. 2020 Dec;34(12):3242-3255. doi: 10.1038/s41375-020-0789-x. Epub 2020 Mar 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


  • Ki-1 Antigen
  • Anaplastic Lymphoma Kinase