The concentrations of interferon (IFN)-β, interleukin (IL)-6, and tumor necrosis factor-α in MM cell culture supernatants were detected with respective commercial ELISA kits.
Loss-of-function mutations in genes encoding the signaling protein tumor necrosis factor receptor-associated factor 3 (TRAF3) are commonly found in human B-cell malignancies, especially multiple myeloma and B-cell lymphoma (BCL).
Noteworthy, a significant inverse correlation of differentially expressed pro-apoptotic genes was observed in pre-MM: overexpression of Fas and TNF-α and underexpression of YY1 versus expression of anti-apoptotic genes in MM: overexpression of YY1 and underexpression of Fas and TNF-α.
In conclusion, blockage of JAK/STAT-mediated NF- κ B activation was highly effective in controlling the growth of MM cells and, consequently, an inhibitor of TNF α -mediated IL-6 secretion would be a potential new therapeutic agent for patients with multiple myeloma.
The aim of this study was to examine the involvement of the tumor necrosis factor-ligand family member, receptor activator of nuclear factor-kappaB ligand (RANKL), and its naturally occurring antagonist, osteoprotegerin (OPG), in MM biology.
For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering part of the LTA*TNF complex (LTA -82C/-90G *TNF -1036C/-487G/-417G, OR = 1.63, 95% CI 1.02-2.16) compared with the most frequently occurring haplotype observed among controls (LTA -82A/-90A *TNF -1036C/-487G/-417G).
Similarly, marrow stromal cells from p62(-/-) mice produced much lower levels of IL-6, tumor necrosis factor-alpha (TNF-alpha), and receptor activator of NF-kappaB ligand (RANKL) and supported MM cell growth and osteoclast formation to a much lower extent than normal cells.
Agents which act to inhibit TNFalpha may therefore abrogate the paracrine growth and survival advantage conferred by MM cell adhesion in the BM microenvironment.
The results of the present study indicate that complement and coagulation-associated genes, the complement and coagulation cascades pathway, EDN1, let-7e, let-7b-5p, miR-19a, and the tumor necrosis factor and HIF-1 signaling pathways may all be implicated in MM and MGUS.
Our results indicate that the cytokine (IL-6, TNF-alpha and IL-1beta) and IL-Ra gene polymorphisms do not confer susceptibility to the development of MM.
CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma.
These findings suggest that regulatory polymorphisms of the TNF-alpha gene can affect TNF-alpha production and predict the outcome after Thal therapy, particularly in those MM pts who are genetically defined as "high producers" of TNF-alpha.
We demonstrate that myeloma stimulates osteoclastogenesis by triggering a coordinated increase in the tumor necrosis factor-related activation-induced cytokine (TRANCE) and decrease in its decoy receptor, osteoprotegerin (OPG).
Knock-down of XBP1 in MM patient BMSCs greatly compromised their increased VCAM-1 protein expression and IL-6 and RANKL secretion in response to TNFα and reversed their enhanced support of MM-cell growth and osteoclast formation.
In the present study we investigated the association of deletion polymorphisms in <i>GSTT1/GSTM1</i> genes and single nucleotide polymorphisms (SNPs) in the <i>TNF-</i>α gene at positions -308/-238 with the risk and outcome in MM and sensitivity to bortezomib under <i>in vitro</i> conditions.
We discovered that among several myeloma growth/survival factors tested (including IL6, oncostatin M, insulin-like growth factor 1, tumor necrosis factor α and IFNα) IFNγ was the strongest inducer of BCL6 mRNA and protein expression in MM cell lines.
B-cell maturation antigen (BCMA), a tumor necrosis factor receptor (TNFR) family member, is selectively expressed on terminally differentiated B-lymphocytes including multiple myeloma (MM) tumor cells.