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Blood, 1 April 2006, Vol. 107, No. 7, pp. 2882-2888.
Prepublished online as a Blood First Edition Paper on November 22, 2005; DOI 10.1182/blood-2005-09-3552.
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Submitted September 2, 2005
Accepted November 9, 2005
B-lymphocyte stimulator (BLyS) stimulates immunoglobulin production and malignant B-cell growth in Waldenstrom's macroglobulinemia
Sherine F Elsawa, Anne J Novak, Deanna M Grote, Steven C Ziesmer, Thomas E Witzig, Robert A Kyle, Stacey R Dillon, Brandon Harder, Jane A Gross, and Stephen M Ansell*
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN, USA
ZymoGenetics Inc, Seattle, WA, USA
* Corresponding author; email: Ansell.stephen{at}mayo.edu.
Waldenstrom's macroglobulinemia (WM) is a serious and frequently fatal B-cell malignancy associated with an elevated monoclonal IgM protein in the serum. Many of the mechanisms leading to this disease are not yet known. BLyS (B-lymphocyte stimulator) is a TNF family member that is critical for maintenance of normal B-cell development and homeostasis. BLyS is overexpressed in a variety of B-cell malignancies and has been shown to inhibit apoptosis in malignant B-cells. It also regulates immunoglobulin secretion by normal B-cells. To determine the relevance of BLyS in WM, we examined the role of BLyS in WM patient samples. Malignant B-cells were found to bind soluble BLyS and variably express the receptors, BAFF-R, TACI and BCMA. We also found expression of BLyS in bone marrow specimens by immunohistochemistry and elevated serum BLyS levels in patients with WM. BLyS, alone or in combination with cytokines that induce immunoglobulin production, was found to increase IgM secretion by malignant B-cells. Furthermore, BLyS was found to increase the viability and proliferation of malignant B-cells from WM patients. Due to the role of BLyS in WM, strategies to inhibit BLyS may potentially have therapeutic efficacy in these patients.
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