WNT974 in combination with nilotinib significantly inhibits regeneration of CML LTHSC after second transplant and prolongs the survival of BCR-ABL mice. (A) BCR-ABL expression was induced in SCL-tTA-BCR-ABL mice by tetracycline withdrawal. BM cells were obtained 3 weeks after induction and transplanted into wild-type FVB/N recipient mice irradiated at 750 cGy (106 cells/mouse; 6-8 mice/group). Three weeks posttransplantation, treatment with vehicle, nilotinib (50 mg/kg), WNT974 (5 mg/kg), or a combination was initiated and continued for 3 weeks. (B) Mice were followed after discontinuation of treatment. (C) BM cells from mice receiving different treatments as described in Figure 4 were pooled and transplanted (2 × 106 cells per mouse; 8-9 mice/group) into wild-type irradiated FVB/N recipient mice for secondary transplantation. Mice were killed after 12 weeks, and the number of BM LTHSC (D), GMP (E), splenic LTHSC (F), and GMP (G) were analyzed. Error bars represent mean ± SEM. *P < .05.
