Developing an in vitro model of T cell type of large granular lymphocyte leukemia

作者：Ren Tong; Yang Jun; Broeg Katie; Liu Xin; Loughran Thomas P Jr; Cheng Hua^*

来源：Leukemia Research, 2013, 37(12): 1737-1743.

DOI：10.1016/j.leukres.2013.10.002

• T-LGLL
• Stat3
• NF kappa B
• Retroviral Tax oncoprotein

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 I kappa B kinases as well as expression of cytotoxic gene products such as granzyme B, perforin and IFN gamma. 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.

• 出版日期2013-12