Upregulation of erythroblast apoptosis by malignant plasma cells: a new pathogenetic mechanism of anemia in multiple myeloma.
Anemia of variable severity occurs in more than two-thirds of patients with multiple myeloma (MM). Besides the altered cytokine network, chronic erythropoietn deficiency, blood loss and hemolysis, we have shown that deregulated myeloma cell apoptosis contributes to progressive destruction of the erythroid matrix by inducing erythroblast cytotoxicity. To exert this effect, highly malignant plasma cells overexpress both Fas-L and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which efficiently trigger the death of immature erythroblasts. However, this Fas-L/TRAIL-based anemia occurs in particular in patients with severely progressive MM, thus suggesting that these apoptogen receptors may characterize a peculiar cytotoxic-apoptogenic phenotype of malignancy. Immunophenotyping of myeloma cells could help to identify patients with a higher risk of erythropoiesis exhaustion.
Silvestris
Franco
F
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari, Italy.
Cafforio
Paola
P
Grinello
Daniela
D
Dammacco
Franco
F
D000740:Anemia / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication; D002454:Cell Differentiation; D018920:Coculture Techniques; D016207:Cytokines / Q000502:physiology; D018450:Disease Progression; D004351:Drug Resistance; D015672:Erythroid Precursor Cells / Q000473:pathology*; D004920:Erythropoiesis; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use; D053222:Fas Ligand Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D009101:Multiple Myeloma / Q000150:complications*; D010950:Plasma Cells / Q000502:physiology*; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; D014407:Tumor Cells, Cultured / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin