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Medline ® Abstract for Reference 54

of 'Clinical manifestations, pathologic features, and diagnosis of T cell large granular lymphocyte leukemia'

Increased serum soluble IL-15Rαlevels in T-cell large granular lymphocyte leukemia.
Chen J, Petrus M, Bamford R, Shih JH, Morris JC, Janik JE, Waldmann TA
Blood. 2012 Jan;119(1):137-43. Epub 2011 Nov 2.
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-15Rαand IL-2/IL-15Rβandγ(c) shared with IL-2. Using a newly developed assay, we demonstrated increased levels of soluble IL-15Rαin the serum of patients with T-LGL leukemia. Furthermore, IL-15RαmRNA levels were also up-regulated in the PBMCs of these patients. FACS analysis indicated that IL-15Rαwas 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-15Rαin T-LGL leukemia. It is conceivable that higher IL-15Rαexpression may lower IL-15 response threshold in vivo and, therefore, may contribute to the pathogenesis of the disease.
Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892-1374, USA.