Elevated serum B-lymphocyte stimulator levels in patients with familial lymphoproliferative disorders

Anne J. Novak, Deanna M. Grote, Steven C. Ziesmer, Michael P. Kline, Michelle K. Manske, Susan Slager, Thomas E. Witzig, Tait Shanafelt, Timothy G. Call, Neil E. Kay, Diane F. Jelinek, James R. Cerhan, Jane A. Gross, Brandon Harder, Stacey R. Dillon, Stephen M. Ansell

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

Purpose: Serum B-lymphocyte stimulator (BLyS) levels have been found to be elevated in a number of immune disease models. Therefore, we sought to establish whether BLyS levels were elevated in patients with B-cell lymphoproliferative disorders and to determine whether elevated BLyS levels correlated with clinical characteristics of the disease. Patients and Methods: Specimens were collected from the peripheral blood of individuals diagnosed with B-cell chronic lymphocytic leukemia (B-CLL; n = 70) or from age- and sex-matched patients seen at the same institution (n = 41). Serum BLyS levels were determined by enzyme-linked immunosorbent assay, and sequencing of the BLyS promoter was performed by conventional methods and confirmed by restriction fragment length polymorphism analysis. Results: We found that elevated BLyS levels were more common in patients with familial B-CLL than individuals with sporadic B-CLL or normal controls. Because of this association, we sequenced the BLyS promoter in patients with B-CLL and normal controls and identified a polymorphic site, -871 C/T. We found that the wild-type sequence was significantly underrepresented in patients with familial B-CLL (4%) compared with patients with sporadic B-CLL (30%; P = .01) or controls (24%; P = .04). Furthermore, using a luciferase reporter under control of the BLyS promoter containing either a C or a T at position -871, we found that the reporter construct containing a T at -871 had a 2.6-fold increase in activity (P = .004). Conclusion: Our data suggest serum BLyS levels are elevated in patients with familial B-CLL and that elevated BLyS levels correlate with the presence of a T at -871 in the BLyS promoter.

Original languageEnglish (US)
Pages (from-to)983-987
Number of pages5
JournalJournal of Clinical Oncology
Volume24
Issue number6
DOIs
StatePublished - Feb 20 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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