title: Increased serum soluble IL-15Rα levels in T-cell large granular lymphocyte leukemia.
abstract: Large granular lymphocyte (LGL) leukemia is a clonal lymphoproliferative disease of mature T and natural killer cells. The etiology of LGL leukemia is unknown. IL-15 is an inflammatory cytokine that stimulates T and natural killer cells and is critical for their survival and proliferation. IL-15 signals through a heterotrimeric receptor that is composed of a private receptor, IL-15Rα and IL-2/IL-15Rβ and γ(c) shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15Rα in the serum of patients with T-LGL leukemia. Furthermore, IL-15Rα mRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15Rα was expressed both on monocytes as well as on some CD8+ leukemic cells of the patients. Interestingly, the mRNA levels of IFN-γ, a known inducer of IL-15Rα, were also up-regulated in patients' PBMCs. Moreover, PBMCs of some T-LGL patients proliferated at higher levels in response to exogenously added IL-15 compared with those of normal donors. In summary, our study demonstrated increased expression of IL-15Rα in T-LGL leukemia. It is conceivable that higher IL-15Rα expression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease.
authors: Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1374, USA.
authors: Jing
authors: J
authors: Chen
authors: Mike
authors: M
authors: Petrus
authors: Richard
authors: R
authors: Bamford
authors: Joanna H
authors: JH
authors: Shih
authors: John C
authors: JC
authors: Morris
authors: John E
authors: JE
authors: Janik
authors: Thomas A
authors: TA
authors: Waldmann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019409:Interleukin-15 / Q000097:blood; D053720:Interleukin-15 Receptor alpha Subunit / Q000097:blood* / Q000235:genetics*; D054066:Leukemia, Large Granular Lymphocytic / Q000097:blood* / Q000235:genetics / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D019409:Interleukin-15; D053720:Interleukin-15 Receptor alpha Subunit; D012333:RNA, Messenger