Originally published as JCO Early Release 10.1200/JCO.2005.02.7938 on January 23 2006

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Elevated Serum B-Lymphocyte Stimulator Levels in Patients With Familial Lymphoproliferative Disorders

From the Division of Hematology and Internal Medicine, Department of Immunology, and Divisions of Epidemiology and Biostatistics, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN; and Zymogenetics, Seattle, WA

Address reprint requests to Stephen M. Ansell, MD, PhD, Division of Hematology and Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905; e-mail: ansell.stephen{at}mayo.edu

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.

Supported in part by Grants No. CA92104 and CA97274 from the National Institutes of Health and a Translational Research Grant from the Leukemia and Lymphoma Society.

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