Dataset Information

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

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.

SUBMITTER: Kreutmair S

PROVIDER: S-EPMC7685983 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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

Kreutmair Stefanie S Klingeberg Cathrin C Poggio Teresa T Andrieux Geoffroy G Keller Alexander A Miething Cornelius C Follo Marie M Pfeifer Dietmar D Shoumariyeh Khalid K Lengerke Claudia C Gonzalez-Menendez Irene I Fend Falko F Zeiser Robert R Turner Suzanne D SD Quintanilla-Martinez Leticia L Boerries Melanie M Duyster Justus J Illert Anna L AL

Leukemia 20200317 12

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-</su ...[more]

PMID: 32203142

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Project description:BackgroundDifferentiated plant cells can retain the capacity to be reprogrammed into pluripotent stem cells during regeneration. This capacity is associated with both cell cycle reactivation and acquisition of specific cellular characters. However, the molecular mechanisms underlying the reprogramming of protoplasts into stem cells remain largely unknown. Protoplasts of the moss Physcomitrella patens easily regenerate into protonema and therefore provide an ideal system to explore how differentiated cells can be reprogrammed to produce stem cells.Principal findingsWe obtained genome-wide digital gene expression tag profiles within the first three days of P. patens protoplast reprogramming. At four time-points during protoplast reprogramming, the transcript levels of 4827 genes changed more than four-fold and their expression correlated with the reprogramming phase. Gene ontology (GO) and pathway enrichment analysis of differentially expressed genes (DEGs) identified a set of significantly enriched GO terms and pathways, most of which were associated with photosynthesis, protein synthesis and stress responses. DEGs were grouped into six clusters that showed specific expression patterns using a K-means clustering algorithm. An investigation of function and expression patterns of genes identified a number of key candidate genes and pathways in early stages of protoplast reprogramming, which provided important clues to reveal the molecular mechanisms responsible for protoplast reprogramming.ConclusionsWe identified genes that show highly dynamic changes in expression during protoplast reprogramming into stem cells in P. patens. These genes are potential targets for further functional characterization and should be valuable for exploration of the mechanisms of stem cell reprogramming. In particular, our data provides evidence that protoplasts of P. patens are an ideal model system for elucidation of the molecular mechanisms underlying differentiated plant cell reprogramming.

Dataset Information

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

Publications

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

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