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Blood, 15 October 2004, Vol. 104, No. 8, pp. 2247-2253.
Prepublished online as a Blood First Edition Paper on July 13, 2004; DOI 10.1182/blood-2004-02-0762.
 Previous Article | Next Article 
Submitted March 1, 2004
Accepted May 26, 2004
Expression of BLyS and Its Receptors in B-Cell Non-Hodgkin Lymphoma: Correlation With Disease Activity and Patient Outcome
Anne J Novak, Deanna M Grote, Mary Stenson, Steven C Ziesmer, Thomas E Witzig, Thomas M Habermann, Brandon Harder, Kay M Ristow, Richard J Bram, Diane F Jelinek, Jane A Gross, and Stephen M Ansell*
Department of Hematology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA
Department of Immunology, Mayo Clinic College of Medicine, Rochester, MN, USA
ZymoGenetics, Seattle, WA, USA
* Corresponding author; email: ansell.stephen{at}mayo.edu.
BLyS, recently shown to be critical for survival of normal B cells, has been found to be elevated in a number of immune disease models. A role for BLyS in the survival of malignant B cells has also been revealed and we therefore sought to identify a role for BLyS and its receptors in non-Hodgkin lymphoma (NHL). We find that tumor cells from all NHL histologic subtypes expressed one or more of three known receptors (BCMA, TACI, and BAFF-R) for BLyS; however, the pattern of expression was variable. We provide evidence that BLyS is expressed in tumors from NHL patients and that BLyS levels increase as tumors transform to a more aggressive phenotype. Additionally, we provide evidence that serum BLyS levels are elevated in a subgroup of NHL patients. In patients with de novo large B-cell lymphoma, a high BLyS level correlated with a poorer median overall survival, the presence of constitutional symptoms, and elevated LDH values. When BLyS levels were correlated with response to therapy in all patients, responding patients had a significantly lower BLyS level than those with progressive disease. In summary, we find that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma.
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