CNTO 530 enhances the formation of PODXL^highCD71^high bone marrow erythroid progenitors. (A) To investigate possible differential effects of CNTO 530 and epoetin-alfa or darbepoietin-alfa on bone marrow erythroid progenitor cell populations, mice were administered each at doses that at day 4 provided near maximum, and highly comparable levels of reticulocyte and red cell production. Near equivalency in reticulocyte production at day 4 was observed after dosing with CNTO 530 (0.15 μg/mouse gram-weight), epoetin-alfa (EPO; 2 U/mouse gram-weight at 1 and 24 hours), or darbepoietin-alfa (0.012 μg/mouse gram-weight). Values for each injected mouse are shown together with mean values (horizontal bars). (B) For bone marrow–resident erythroid progenitors, CNTO 530 induced significant increases in the intensity (ie, cell surface density) of PODXL expression. Here, this is shown in representative flow cytometric analyses that compare PODXL expression levels after CNTO 530 versus EPO dosing, and CNTO 530 versus darbepoietin-alfa. (C) At days 2, 4, and 6, frequencies of PODXL^highCD71^high progenitors within bone marrow were determined by flow cytometry. Top panels illustrate representative flow cytometry analyses and demonstrate a clear advantage for CNTO 530 in stimulating the formation of this PODXL^highCD71^high erythroid progenitor cell pool, especially at days 4 and 6. Mean frequencies (± SE) of such PODXL^highCD71^high progenitors are graphed as analyzed in n = 3 mice after CNTO 530, EPO, or darbepoietin-alfa injections. (EPO was administered at 1 and 24 hours.) (D) Gating on, or off, Ter119^posCD71^high erythroid progenitors revealed that CNTO 530's effects on enhanced PODXL expression was exerted among not only later stage Ter119^pos cells, but also their CD71^highTer119^neg progenitors. Values are means ± SE (n = 3).