T-cell lymphomas in T-cell-specific Pten-deficient mice originate in the thymus View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-11-29

AUTHORS

T J Hagenbeek, H Spits

ABSTRACT

Phosphatase and tensin homolog deleted on chromosome 10 (Pten) is a tumor suppressor protein whose loss of lipid phosphatase activity is associated with lymphomagenesis. We made use of the Cre-loxP system to delete Pten expression in Lck- or CD4-expressing T-lineage cells. Mice initially showed modest thymic hyperplasia and subsequently developed expanding and infiltrating T-cell lymphomas, leading to a premature death within 5 to 23 weeks. Frequently, all thymocyte and peripheral T-cell populations displayed phenotypes characteristic for immature developing thymocyte precursors and shared elevated levels of clonally rearranged T-cell receptor (TCR) β chains. In concert, CD2, CD5, CD3ɛ and CD44, proteins associated with increased expression and signaling capacity of both the immature pre-TCR and the mature αβTCR, were more abundantly expressed, reflecting a constitutive state of activation. Although most T-cell lymphomas had acquired the capability to infiltrate the periphery, not all populations left the thymus and expanded clonally exclusively in the thymus. In line with this, only transplantation of thymocytes with infiltrating capacity gave rise to T-cell lymphoma in immunodeficient recipients. These results indicate that T-cell-specific Pten deletion during various stages of thymocyte development gives rise to clonally expanding T-cell lymphomas that frequently infiltrate the periphery, but originate in the thymus. More... »

PAGES

608-619

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.leu.2405056

DOI

http://dx.doi.org/10.1038/sj.leu.2405056

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1019003933

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/18046443


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