RAP-536 promotes erythroid differentiation in Hbbth1/th1 mice. (A) Representative flow cytometric density plots for Ter119+ erythroid precursors from bone marrow (BM) and spleen separated into basophilic erythroblasts (R1), late basophilic and polychromatic erythroblasts (R2), and orthochromatic reticulocytes and reticulocytes (R3) on the basis of CD71 expression and cell size (Fsc, forward scatter) as previously described.21 Hbbth1/th1 mice (3-4 months old) were treated with RAP-536 (1 mg/kg, s.c.) or vehicle twice weekly for 2 months. (B) Quantitative flow cytometric data of erythroid precursors from bone marrow and spleen indicate that RAP-536 reduced the proportion of cells in R1 and R2 and concurrently increased the proportion in R3 compared with vehicle. n = 5 to 7 mice per group. (C) Serum EPO concentrations (n = 6-11 mice per group). (D) (Left) Spleen weight (n = 13-17 mice per group). (Right) Spleen size shown in representative images obtained in a study separate from that shown at left but using the same dosing schedule in 10- to 12-month-old mice. Data in B to D are means ± SEM. *P < .05 and **P < .01, RAP-536 vs vehicle; ###P < .001 vs wild type.
