title: The pathogenesis and treatment of large granular lymphocyte leukemia.
abstract: Large granular lymphocyte (LGL) leukemia is a spectrum of rare lymphoproliferative diseases of T lymphocytes and natural killer cells. These diseases frequently present with splenomegaly, neutropenia, and autoimmune diseases like rheumatoid arthritis. LGL leukemia is more commonly of a chronic, indolent nature; however, rarely, they have an aggressive course. LGL leukemia is thought to arise from chronic antigen stimulation, which drives long-term cell survival through the activation of survival signaling pathways and suppression of pro-apoptotic signals. These include Jak-Stat, Mapk, Pi3k-Akt, sphingolipid, and IL-15/Pdgf signaling. Treatment traditionally includes immunosuppression with low dose methotrexate, cyclophosphamide, and other immunosuppressive agents; however, prospective and retrospective studies reveal very limited success. New studies surrounding Jak-Stat signaling suggest this may reveal new avenues for LGL leukemia therapeutics.
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Steven Nathaniel
authors.initials: SN
authors.lastname: Steinway
authors.affiliation: Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: LeBlanc
authors.affiliation: University of Virginia Cancer Center, University of Virginia, Charlottesville, VA, USA. Electronic address: TL7CS@hscmail.mcc.virginia.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Loughran
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D054066:Leukemia, Large Granular Lymphocytic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged
keywords: Cell signaling; Large granular lymphocyte leukemia; Pathogenesis