Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atacicept, a fully human recombinant fusion protein that blocks the activity of BLyS (B-Lymphocyte Stimulator) and APRIL (a proliferation-inducing ligand), is undergoing clinical evaluation in B-cell-mediated diseases, including autoimmune disorders. Nonclinical studies in mice and cynomolgus monkeys demonstrate dose-dependent, reversible decreases in circulating Ig concentrations and reductions in mature B cells in the peripheral blood and lymphoid tissues. However, the combination of atacicept with purine synthesis inhibitors (e.g., mycophenolate mofetil [MMF]) and anti-B-cell monoclonal therapy (e.g., rituximab) has not been evaluated. Atacicept does not augment hematological toxicities associated with MMF, including anemia or thrombocytopenia. Combination of atacicept with MMF or rituximab reduced B cells in the periphery (MMF) or tissues (MMF and rituximab) further than did monotherapy, as was the case with atacicept-MMF combination therapy and serum Ig concentrations. Overall, atacicept appears to augment the pharmacologic activity toward B cells of current immunosuppressive therapies without increasing the hematological toxicities associated with MMF. Enhanced reduction in B cells and Ig concentrations associated with atacicept combination therapy may increase therapeutic activity or allow dose reduction in autoimmune patients. Findings from nonclinical safety studies support clinical evaluation of atacicept combination therapies.
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PMID:Preclinical support for combination therapy in the treatment of autoimmunity with atacicept. 1917 29

BLyS is involved in CLL biology and its low soluble serum levels related to a shorter time to first treatment (TFT). TACI is a BLyS receptor and can be shed from cells' surface and circulate in soluble form (sTACI). We investigated the impact of serum BLyS and sTACI levels at diagnosis in CLL patients and their relationship with disease parameters and patients' outcome. Serum BLyS was determined in 73 patients, while sTACI in 60. Frozen sera drawn at diagnosis were tested by ELISA. sTACI concentrations correlated with BLyS (P = -0.000021), b2-microglobulin (P = 0.005), anemia (P = -0.03), thrombocytopenia (P = 0.04), Binet stage (P = 0.02), and free light chains ratio (P = 0.0003). Soluble BLyS levels below median and sTACI values above median were related to shorter TFT (P = 0.0003 and 0.007). During a ten-year followup, sTACI levels, but not BLyS, correlated with survival (P = 0.048). In conclusion, we confirmed the prognostic significance of soluble BLyS levels with regard to TFT in CLL patients, and, more importantly, we showed for the first time that sTACI is a powerful prognostic marker, related to parameters of disease activity and staging and, more importantly, to TFT and OS.
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PMID:Serum soluble TACI, a BLyS receptor, is a powerful prognostic marker of outcome in chronic lymphocytic leukemia. 2516 1