BLyS Levels Elevated in Familial CLL

January 27, 2006

J Clin Oncol. 2006 Jan 23; [Epub ahead of print]

Elevated Serum B-Lymphocyte Stimulator Levels in Patients With

Familial Lymphoproliferative Disorders.

Novak AJ, Grote DM, Ziesmer SC, Kline MP, Manske MK, Slager S, Witzig

TE, Shanafelt T, Call TG, Kay NE, Jelinek DF, Cerhan JR, Gross JA,

Harder B, Dillon SR, Ansell SM.

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.

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.

PMID: 16432079 [PubMed - as supplied by publisher]

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