Romiplostim sensitizes HS(P)Cs to CyBu chemotherapy in a preclinical HSCT model and allows a dose reduction of busulfan while maintaining a stable long-term chimerism. (A) The experimental setup to assess the effects of RPL on chemosensitivity to CyBu conditioning therapy in functionally defined long-term HSCs; animals were treated with RPL/PBS and cyclophosphamide and busulfan as also described in Figure 1D but in contrast received BM transplant after their course of chemotherapy. Experimental animals were followed for 14 weeks and bled regularly before their BM was analyzed and transplanted into secondary recipients and observed there for another 16 weeks. The peripheral blood donor leukocyte chimerism (CD45.1/CD45.2) (B) and the donor granulocyte chimerism (CD45.1/CD45.2 CD11b⁺Ly-6C/G⁺) (C) in primary transplant recipient mice. (D-E) The phenotypic HSPC and HSC chimerisms of primary transplant recipients 14 weeks after primary transplantation. (F-G) The peripheral blood donor leukocyte and donor granulocyte chimerisms in secondary transplant recipient mice. (H-I) The BM HSPC and HSC chimerisms of secondary transplant recipient mice. The number of mice used for this experimental setup is depicted in supplemental Figure 2J. ctrl, control; ncc, nonconditioned control; TBI, total body irradiation.