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  • Title: T cell large granular lymphocyte leukemia and chronic NK lymphocytosis.
    Author: Barilà G, Calabretto G, Teramo A, Vicenzetto C, Gasparini VR, Semenzato G, Zambello R.
    Journal: Best Pract Res Clin Haematol; 2019 Sep; 32(3):207-216. PubMed ID: 31585621.
    Abstract:
    Large Granular Lymphocyte Leukemia (LGLL) is a rare chronic lymphoproliferative disorder characterized by the clonal expansion of Large Granular Lymphocytes (LGLs). Among LGLL, the 2016 WHO classification recognizes two different entities, i.e. T-LGLL and the provisional entity Chronic Lymphoproliferative disorder of NK cells (CLPD-NK). In both subtypes neutropenia represents the hallmark of the disease and is frequently regarded as the leading reason to start treatment. Leukemic LGLs are characterized by the up-regulation of several pro-survival signaling pathways, the most relevant being the JAK-STAT axis, whose constitutive activation is partly explained by somatic mutations in STAT3 and STAT5b. In addiction, in the last few years, a relationship between STAT3 mutations/activation and the development of neutropenia was found. Given that backbone treatment relying on immunosuppressive agents is generally unsatisfactory, novel agents targeting the JAK/STAT pathway can represent a turning point in LGLL treatment.
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