Abstract
The expression of proteins of the tumor necrosis factor (TNF) family on erythroblasts was measured during thalidomide treatment in 29 patients with multiple myeloma (MM). A clinical response was observed in 17 patients (58.6%) and haemoglobin concentration increased in 22 patients (75.9%). The expression of FasL, Fas, TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL-R1 on erythroblasts decreased significantly during thalidomide treatment. Additional in vitro studies revealed that the apoptosis of erythroblasts and the expression of FasL, TRAIL, TRAIL-R1 and TRAIL-R2 was lower in cultures with thalidomide than in control cultures. Altogether our results suggest that thalidomide may stimulate erythropoiesis in MM patients by decreasing the expression of TNF-like ligands/receptors on erythroblasts.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Apoptosis Regulatory Proteins / antagonists & inhibitors
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Apoptosis Regulatory Proteins / biosynthesis*
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Apoptosis Regulatory Proteins / blood
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Erythroblasts / drug effects
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Erythroblasts / metabolism*
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Erythropoiesis / drug effects*
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Erythropoiesis / physiology
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Fas Ligand Protein
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Female
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Humans
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Male
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / blood
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Middle Aged
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Multiple Myeloma / drug therapy*
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Multiple Myeloma / metabolism
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / antagonists & inhibitors
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / blood
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TNF-Related Apoptosis-Inducing Ligand
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Thalidomide / pharmacology*
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Thalidomide / therapeutic use
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factors / biosynthesis*
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Tumor Necrosis Factors / blood
Substances
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Apoptosis Regulatory Proteins
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10A protein, human
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TNFRSF10B protein, human
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha
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Tumor Necrosis Factors
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Thalidomide