title: Developing an in vitro model of T cell type of large granular lymphocyte leukemia.
abstract: We developed a strategy that can prolong in vitro growth of T cell type of large granular lymphocyte (T-LGL) leukemia cells. Primary CD8+ lymphocytes from T-LGL leukemia patients were stably transduced with the retroviral tax gene derived from human T cell leukemia virus type 2. Expression of Tax overrode replicative senescence and promoted clonal expansion of the leukemic CD8+ T cells. These cells exhibit features characteristic of leukemic LGL, including resistance to FasL-mediated apoptosis, sensitivity to the inhibitors of sphingosine-1-phosphate receptor and IκB kinases as well as expression of cytotoxic gene products such as granzyme B, perforin and IFNγ. Collectively, these results indicate that this leukemia cell model can duplicate the main phenotype and pathophysiological characteristics of the clinical isolates of T-LGL leukemia. This model should be useful for investigating molecular pathogenesis of the disease and for developing new therapeutics targeting T-LGL leukemia.
authors.affiliation: Penn State Hershey Cancer Institute, Penn State University College of Medicine, Hershey, PA 17033, United States.
authors.forename: Tong
authors.initials: T
authors.lastname: Ren
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Katie
authors.initials: K
authors.lastname: Broeg
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
authors.forename: Hua
authors.initials: H
authors.lastname: Cheng
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D016355:Genes, pX / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D054066:Leukemia, Large Granular Lymphocytic / Q000473:pathology*; D008954:Models, Biological; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D014162:Transfection; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D011948:Receptors, Antigen, T-Cell; D049452:Green Fluorescent Proteins
keywords: NF-κB; Retroviral Tax oncoprotein; Stat3; T-LGLL