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  • Title: Large granular lymphocyte leukemia: from dysregulated pathways to therapeutic targets.
    Author: Leblanc F, Zhang D, Liu X, Loughran TP.
    Journal: Future Oncol; 2012 Jul; 8(7):787-801. PubMed ID: 22830400.
    Abstract:
    Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disorder of cytotoxic lymphocytes characterized by an expansion of CD3(+) cytotoxic T lymphocytes or CD3(-) natural killer cells. Patients present with various cytopenias including neutropenia, anemia and thrombocytopenia. In addition, there is an association of T-cell large granular lymphocytic leukemia with rheumatoid arthritis. It is believed that LGL leukemia begins as an antigen-driven immune response with subsequent constitutive activation of cytotoxic T lymphocytes or natural killer cells through PDGF and IL-15 contributing to their survival. Consequently, this leads to a dysregulation of apoptosis and dysfunction of the activation-induced cell death pathway. Treatment of LGL leukemia is based on a low-dose immunosuppressive regimen using methotrexate or cyclophosphamide. However, no standard of therapy has been established, as large prospective trials have not been conducted. In addition, some patients are refractory to treatment. The lack of a curative therapy for LGL leukemia means that new treatment options are needed. Insight into the various dysregulated signaling pathways in LGL leukemia may provide novel therapeutic treatment modalities.
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