Single cell RNA-seq analysis of the effects of idasanutlin and/or nilotinib on primary human CML cells engrafted into the bone marrow of immunocompromised mice

Single cell RNA-seq was performed on primary human CML cells engrafted into the bone marrow of immunocompromised mice to understand the molecular consequences of treatment with the tyrosine kinase inhibitor nilotinib alone and in combination with the MDM2 inhibitor idasanutlin. Overall design: CML CD34+ cells were engrafted into the BM of irradiated immuno-compromised mice (cohort sizes 3 mice per arm per experiment). Eight to twelve weeks post-transplantation, mice were treated with nilotinib (NIL) (50 mg/kg QD) for 7-14 days after which the cohorts received NIL for a further 14 days +/- IDASA (150 mg/kg BD) for the first 5 days. At the end of 28 day treatment or after a further 28 days treatment-free period mice were analyzed for human cell engraftment in the murine bone marrow and scRNA-seq was performed on huCD45+ or huCD34+ cells.