Linking anemia to inflammation and cancer: the crucial role of TNFalpha.
Erythropoiesis is considered as a multistep and tightly regulated process under the control of a series of cytokines including erythropoietin (Epo). Epo activates specific signaling pathways and leads to activation of key transcription factors such as GATA-1, in order to ensure erythroid differentiation. Deregulation leads to a decreased number of red blood cells, a hemoglobin deficiency, thus a limited oxygen-carrying capacity in the blood. Anemia represents a frequent complication in various diseases such as cancer or inflammatory diseases. It reduces both quality of life and prognosis in patients. Tumor necrosis factor alpha (TNFalpha) was described to be involved in the pathogenesis of inflammation and cancer related anemia. Blood transfusions and erythroid stimulating agents (ESAs) including human recombinant Epo (rhuEpo) are currently used as efficient treatments. Moreover, the recently described conflicting effects of ESAs in distinct studies require further investigations on the molecular mechanisms involved in TNFalpha-caused anemia. The present study aims to evaluate the current knowledge and the importance of the effect of the proinflammatory cytokine TNFalpha on erythropoiesis in inflammatory and malignant conditions.
Buck
Isabelle
I
Laboratoire de Biologie Moléculaire et Cellulaire du Cancer (LBMCC), Fondation Recherche Cancer et Sang, Hôpital Kirchberg, 9, rue Edward Steichen, L-2540 Luxembourg, Luxembourg.
Morceau
Franck
F
Grigorakaki
Christina
C
Dicato
Mario
M
Diederich
Marc
M
D000740:Anemia / Q000097:blood* / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D016207:Cytokines / Q000276:immunology; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000378:metabolism; D009369:Neoplasms / Q000097:blood* / Q000150:complications / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000502:physiology*
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin