Figure 6.
BMN673 exerted an anti-MPN xenograft effect in vivo. (Panel A) Experimental model. Sublethally irradiated NRGS recipient mice were injected with 106 primary Lin− MPN cells from individual MPN patients expressing JAK2(V617F), CALR(del52), or MPL(W515L). One week later, mice were treated with vehicle (C), hydroxyurea (H; 30 mg/kg twice daily IP) plus ruxolitinib (R; 30 mg/kg twice daily oral gavage) (HR), BMN673 (B; 0.33 mg/kg IV), and HR+B (HRB) for 3 weeks (3-5 mice per group). Indicated cells were detected by immunofluorescence. (Panel B) Percentage of hCD45+ cells was measured in peripheral blood leukocytes (PBLs), splenocytes (SPLs), and bone marrow cells (BMCs). Number of hCD45+ BMCs expressing Lin−CD34+ and Lin−CD34+CD38− per 106 cells was determined. *P < .05 and **P < .05 in comparison with C and all other groups, respectively, using the Student t test.