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: Tong Ren, Jun Yang, Katie Broeg, Xin Liu, Thomas P Loughran Jr, Hua Cheng
• Journal: Leukemia research (Leuk Res) Vol. 37 Issue 12 Pg. 1737-43 (Dec 2013) ISSN: 1873-5835 [Electronic] England
• PMID: 24183305 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Receptors, Antigen, T-Cell
• Green Fluorescent Proteins

Topics

• CD8-Positive T-Lymphocytes (metabolism, pathology)
• Cell Line, Transformed
• Cell Transformation, Viral (genetics)
• Cytotoxicity, Immunologic (genetics)
• Genes, pX (physiology)
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Jurkat Cells
• Leukemia, Large Granular Lymphocytic (pathology)
• Models, Biological
• Receptors, Antigen, T-Cell (genetics)
• Transfection
• Transgenes
• Tumor Cells, Cultured