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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.
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CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
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
From the Division of Hematology and Internal Medicine, Department of Immunology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN; and ZymoGenetics, Seattle WA.
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 found that tumor cells from all NHL histologic subtypes expressed one or more of 3 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 patients with NHL 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 patients with NHL. 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 values of lactic dehydrogenase. 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 found that BLyS and its receptors represent a potentially important therapeutic target in B-cell lymphoma.
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