Expression of BLyS and its receptors in B-cell non-Hodgkin lymphoma: correlation with disease activity and patient outcome

Abstract

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.

The absolute monocyte and lymphocyte prognostic score predicts survival and identifies high-risk patients in diffuse large-B-cell lymphoma

“…Finally, monocytes are an important source of soluble mediators, like B-lymphocyte stimulator, that support the growth and survival of both normal and malignant B cells. [51][52][53] Not surprisingly then, monocytes have been convincingly shown to support the growth of malignant lymphocytes in both T-and B-cell NHL. 26,54 The vast majority of DLBCL originate from either germinalcenter B cells (that is, GCB type) or from B cells with a geneexpression profile resembling activated B cells (that is, ABC type).…”

Constitutive NF-κB and NFAT activation leads to stimulation of the BLyS survival pathway in aggressive B-cell lymphomas

“…[6][7][8] BLyS is expressed in a cell membrane bound or soluble form [1][2][3][4] by various cell types, including dendritic cells, monocytes, macrophages, activated T cells, neutrophils, and antigen-presenting cells. [1][2][3][4][9][10][11][12][13][14][15][16][17][18][19] Cytokines such as interleukin 10 (IL-10), interferon ␥ (IFN-␥), and IFN-␣ augment BLyS expression in monocytes, macrophages, and dendritic cells, while CD40 ligand stimulates BLyS secretion from dendritic cells. 19 BLyS levels are elevated in the serum of non-Hodgkin lymphoma (NHL) patients and have been reported to be associated with disease activity progression and patient prognosis.…”

“…19 BLyS levels are elevated in the serum of non-Hodgkin lymphoma (NHL) patients and have been reported to be associated with disease activity progression and patient prognosis. 13 Several studies have shown that malignant B cells from NHL-B and multiple myeloma (MM) patients also express abnormal levels of BLyS protein, which protects malignant B cells from spontaneous apoptosis and myeloma cells from apoptosis induced by IL-6 deprivation or dexamethasone. 9,11,12,20,21 In addition to its antiapoptotic activity in malignant B cells, BLyS also promotes MM cell survival.…”

The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors

“…It is therefore necessary to explore the role of BAFF in NHL. It was found in some studies [14] that BAFF mRNA was expressed in the peripheral blood and tumor tissue of NHL patients. Ju et al [15] found that the expression level of BAFF mRNA in the peripheral blood of NHL patients was no higher than that of normal controls; however, their blood specimens were selected from NHL patients who had received medical treatment.…”