Impact of growth factors in the regulation of apoptosis in low-risk myelodysplastic syndromes.
Increased apoptosis of hematopoietic progenitors is a hallmark of myelodysplastic syndromes (MDS) and results in ineffective hematopoiesis. Erythroid apoptosis is thought to be the main mechanism underlying the severe anemia observed in the low-risk subgroups, refractory anemia (RA) and RA with ringed sideroblasts (RARS). Treatment with erythropoietin (Epo) alone or in combination with granulocyte colony-stimulating factor (G-CSF) may significantly improve anemia and reduce bone marrow apoptosis. A synergistic effect between Epo and G-CSF has been observed in the clinic, in particular in RARS. However, the molecular mechanisms beyond the anti-apoptotic effect of these growth factors have not been fully understood. This paper outlines the potential mechanisms underlying the augmented apoptosis during the erythroid differentiation in low-risk MDS as well as the anti-apoptotic effect of the growth factors.
Tehranchi
R
R
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, SE-22184 Lund, Sweden. Ramin.Tehranchi@stemcell.lu.se
D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation; D004272:DNA, Mitochondrial / Q000235:genetics; D004921:Erythropoietin / Q000494:pharmacology* / Q000627:therapeutic use; D005293:Ferritins / Q000235:genetics; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D006410:Hematopoiesis; D006801:Humans; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000473:pathology; D011379:Prognosis
D004272:DNA, Mitochondrial; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D005293:Ferritins