Stimulation of Erythropoiesis by Thalidomide in Multiple Myeloma Patients: Its Influence on FasL, TRAIL and Their Receptors on Erythroblasts and Plasma Cells.

Proteins belonging to the TNF-family, i.e. Fas ligand (FasL), Fas, TRAIL, TRAIL receptor 1 (TRAIL-R1) and TRAIL receptor 2 (TRAIL-R2), are involved in the pathogenesis of anaemia in multiple myeloma patients. Thalidomide (THAL) is successfully used in the treatment of multiple myeloma (MM) and response is usually accompanied by an increase in haemoglobin concentration. In our previous study comprising 234 MM patients treated with THAL we observed that in the group of non-responders more than 50% of patients had improved hemoglobin level after 3 months of treatment. In the present study 29 patients with refractory/relapsed MM were treated with THAL in an initial dose of 100 mg daily, increased to 400 mg. We measured the expression of the erythropoietin receptor (EPOR) and proteins belonging to the TNF-family on erythroblasts as well as the expression of the TNF-family proteins on monoclonal plasmocytes using flow cytometry before and after 3 months of treatment. Erythroblasts and plasma cells were also investigated in short-term cultures of bone marrow mononuclear cells of MM patients. A clinical response was observed in 17 patients (58.6%), but haemoglobin concentration increased in 20 patients (75.9%). An increase in haemoglobin concentration was observed in 12 patients responding to THAL and in 10 patients not responding. The expression of FasL, Fas, TRAIL and TRAIL-R1 decreased significantly during THAL treatment, whereas the expression of EPOR and TRAIL-R2 did not change significantly. In vitro studies revealed that the expression of FasL, TRAIL, TRAIL-R1 and TRAIL-R2 was lower in THAL cultures than in control cultures. The expressions of TNF-like receptors/ligands on monoclonal plasmocytes did not differ significantly between cultures with and without THAL. Altogether our results suggest that THAL may stimulate erythropoiesis and increase haemoglobin level in MM patients and the way in which THAL acts may be connected with a decrease in the expression of TNF-like ligands/receptors on erythroblasts.