title: LGL leukemia: from pathogenesis to treatment.
abstract: Large granular lymphocyte (LGL) leukemia has been recognized by the World Health Organization classifications amongst mature T-cell and natural killer (NK) cell neoplasms. There are 3 categories: chronic T-cell leukemia and NK-cell lymphocytosis, which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK-cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation, which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, phosphatidylinositol 3-kinase-Akt, Ras-Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid, and nuclear factor-κB. Socs3 downregulation may also contribute to Stat3 activation. Interleukin 15 plays a key role in activation of leukemic LGL. Several somatic mutations including Stat3, Stat5b, and tumor necrosis factor alpha-induced protein 3 have been demonstrated recently in LGL leukemia. Because these mutations are present in less than half of the patients, they cannot completely explain LGL leukemogenesis. A better mechanistic understanding of leukemic LGL survival will allow future consideration of a more targeted therapeutic approach than the current practice of immunosuppressive therapy.
authors.affiliation: Department of Hematology, Pontchaillou University Hospital, Rennes, France.|Clinical Investigation Center 1414 INSERM, Rennes, France; and.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.affiliation: Department of Hematology, Pontchaillou University Hospital, Rennes, France.|Clinical Investigation Center 1414 INSERM, Rennes, France; and.
authors.forename: Aline
authors.initials: A
authors.lastname: Moignet
authors.affiliation: University of Virginia Cancer Center, Charlottesville, VA.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
mesh_terms: D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000235:genetics / Q000473:pathology / Q000628:therapy