Increased serum soluble IL-15Rα levels in T-cell large granular lymphocyte leukemia

Jing Chen, Mike Petrus, Richard Bamford, Joanna H. Shih, John C. Morris, John Edward Janik, Thomas A. Waldmann

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31 Scopus citations

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, themRNA levels of IFN-α, 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.

Original languageEnglish (US)
Pages (from-to)137-143
Number of pages7
JournalBlood
Volume119
Issue number1
DOIs
Publication statusPublished - Jan 5 2012

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Chen, J., Petrus, M., Bamford, R., Shih, J. H., Morris, J. C., Janik, J. E., & Waldmann, T. A. (2012). Increased serum soluble IL-15Rα levels in T-cell large granular lymphocyte leukemia. Blood, 119(1), 137-143. https://doi.org/10.1182/blood-2011-04-346759