Responsiveness of bone marrow erythropoietic stem cells (CFU‐E and BFU‐E) to recombinant human erythropoietin (rh‐Ep) in vitro in aplastic anemia and myelodysplastic syndrome

Abstract

Responsiveness of bone marrow erythropoietic stem cells (CFU-E and BFU-E) to recombinant human erythropoietin (rh-Ep) was examined in vitro in 23 patients with aplastic anemia and 14 with myelodysplastic syndrome (MDS) to investigate the clinical use of rh-Ep for these diseases. Bone marrow mononuclear cells were cultured by methylcellulose methods for CFU-E and BFU-E assays. In normals, the CFU-E numbers reached a plateau of increase at Ep doses of almost 2-5 units, and no further increase was observed with the addition of larger Ep doses. In aplastic anemia, the responses of CFU-E to Ep were relatively good in nonsevere type and generally poor in severe type. However, the CFU-E numbers increased with increasing doses of Ep in some of the patients with aplastic anemia. Among the patients with MDS, the responses of CFU-E to Ep were relatively good in primary acquired refractory anemia (PARA) and primary acquired sideroblastic anemia. On the other hand, the responses of CFU-E to Ep were poor in refractory anemia with an excess of blasts (RAEB) and RAEB in transformation among the MDS patients. BFU-E responses to Ep were poor in severe aplastic anemia, RAEB, and RAEB-T. However, there are Ep responsive patients in some of aplastic anemia and PARA. High titers of rh-Ep were suggested to be effective clinically in some patients with aplastic anemia and those with PARA.

Subcutaneous Recombinant Human Erythropoietin for the Treatment of Anemia in Myelodysplastic Syndromes

“…Here again differences in composition of study populations and in culture techniques might account for 63 the conflicting results obtained. Actually, a significant in crease in the number of erythroid progenitors in response to high levels of rhEPO has been observed in vitro in a sub set of MDS patients [27]. These findings confirm that at least in some MDS patients EPO-sensitive progenitor cells are present and arc able to respond to pharmacolog ical doses of rhEPO.…”

Characterization of the erythropoiesis in myelodysplasia by means of ferrokinetic studies, in vitro erythroid colony formation and soluble transferrin receptor

“…Several in vitro studies have shown that erythroid progenitors in vitro do not expand in response to epo or epo plus MGF stimulation. [2][3][4][5][6][7][8] Also the in vivo treatment of MDS patients with rhEPO is of limited benefit. [25][26][27] However, in spite of the limited in vitro proliferative capacity of the erythroid progenitor cell, a normal or increased number of normoblasts are observed in the bone marrow suggesting that in vivo the differentiation pathway is not totally blocked.…”

“…Several in vitro studies have shown that BFU-E and CFU-E do not expand in response to erythropoietin (Epo) or Epo plus mast cell growth factor (MGF). [2][3][4][5][6][7][8] Moreover a differentiation block is observed at the level of early erythroid progenitor cell which is frequently associated with the aberrant expression of Evi-1. 9 The Evi-1 gene encodes a zinc finger protein that functions as transcription factor.…”

In vitro proliferation and differentiation of erythroid progenitors from patients with myelodysplastic syndromes: evidence for Fas-dependent apoptosis

“…Several in vitro culture studies using unsorted bone marrow mononuclear cells from patients with MDS found that erythroid progenitors such as erythroid burst-forming units (BFU-Es) and erythroid colony-forming units (CFU-Es) did not expand correctly in response to erythropoietin (Epo) alone or to a mixture of Epo, stem cell factor (SCF), and interleukin-3 (IL-3). [1][2][3] In most patients with MDS, BFU-Es also failed to emerge from sorted CD34 ϩ CD36 Ϫ cells. 4 Proliferation of CD34 ϩ and CD34 ϩ CD38 Ϫ progenitors in serum-free medium was impaired, despite optimal concentrations of SCF, flt-3 ligand, thrombopoietin, IL-3, granulocyte colony-stimulating factor, granulocytemacrophage colony-stimulating factor (GM-CSF), and Epo.…”