Ineffective Erythropoiesis (IE)

IE is characterized by increased proliferation of erythroid progenitor cells, abnormal differentiation, impaired maturation, and increased cell death, resulting in reduced functional red blood cells (RBCs) and anemia.1,2

  • The combination of increased proliferation and reduced differentiation results in a net increase of erythroid progenitors1
  • During IE, increased proliferation due to raised erythropoietin (EPO) levels causes enhanced survival of erythroid progenitors (colony-forming units–erythroid [CFU-Es]/proerythroblasts) in the bone marrow1,2
  • IE is a significant contributor to anemia in myelodysplastic syndromes (MDS),3 with several underlying mechanisms:
    • EPO-driven hyperproliferation of erythroid progenitor cells, which undergo cell death in the bone marrow4
    • Abnormal differentiation and impaired erythroid maturation1,2
    • Disordered iron metabolism with low hepcidin levels, and a blunting of the response to iron overload3
    • Patients with MDS have elevated levels of growth differentiation factor 11 (GDF11, a member of the transforming growth factor beta [TGF-β] family), which has a suggested inhibitory role in differentiation and erythroid maturation3

IE is a significant contributor to anemia in MDS, as well as iron overload in some patients.3

References: 1. Oikonomidou PR, Rivella S. What can we learn from ineffective erythropoiesis in thalassemia? Blood Rev. 2018;32(2):130-143. 2. Gupta R, Musallam KM, Taher AT, Rivella S. Ineffective erythropoiesis: anemia and iron overload. Hematol Oncol Clin North Am. 2018;32(2):213-221. 3. Moukalled NM, El Rassi FA, Temraz SN, Taher AT. Iron overload in patients with myelodysplastic syndromes: an updated overview. Cancer. 2018;124(20):3979-3989. 4. Raj K, Mufti GJ. The myelodysplastic syndromes. In: Hoffbrand AV, Higgs DR, Keeling DM, Mehta AB, eds. Postgraduate Haematology. Chichester, West Sussex: John Wiley & Sons, Ltd; 2016:438-473.