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  • Title: Diseases of large granular lymphocytes.
    Author: Alekshun TJ, Sokol L.
    Journal: Cancer Control; 2007 Apr; 14(2):141-50. PubMed ID: 17387299.
    Abstract:
    BACKGROUND: Clonal diseases of large granular lymphocytes (LGLs) are rare lymphoproliferative malignancies that arise from either mature T-cell (CD3+) or natural killer (NK)-cell (CD3-) lineages. They manifest a distinct biologic behavior that ranges from indolent to very aggressive. METHODS: We discuss four distinct diseases involving LGLs: indolent T-cell LGL leukemia, aggressive T-cell LGL leukemia, chronic NK-cell leukemia, and aggressive NK-cell leukemia. Furthermore, we present an up-to-date systematic review of therapies for each entity. RESULTS: Sustained LGLs, characteristic immunophenotype, clonal origin of leukemic cells, and clinical presentation are the most important features that distinguish indolent from aggressive subtypes of LGL leukemia and guide the selection of therapy. Patients with symptomatic indolent T-cell or NK-cell LGL leukemia are usually treated with immunosuppressive therapies in contrast to aggressive T-cell and NK-cell LGL leukemia, which require intensive chemotherapy induction regimens. Novel targeted therapies using monoclonal antibodies against receptors, including CD2, CD52, the beta subunit of the interleukin-2 receptor, and small molecules such as tipifarnib, are undergoing evaluation in clinical trials. CONCLUSIONS: Future scientific advances focusing on the delineation of molecular pathogenic mechanisms and the development of new targeted therapies for each distinct LGL leukemia entity should lead to improved outcomes of patients with these disorders.
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