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. 2019 Aug 1;105(5):1274–1284. doi: 10.3324/haematol.2019.219261

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Effects of combined activation of p53 by MDM2 inhibition and inhibition of BCR-ABL1 by imatinib in vivo. (A) Experimental scheme. (B) The combination of the MDM2 inhibitor DS-5272 (DS) and imatinib (IM) significantly decreases chronic myeloid leukemia (CML) lineage-SCA-1⁺C-KIT⁺ (LSK) frequency, increases p53 signaling in CML LSK cells, and reduces leukemia cells in various cell subsets in mouse bone marrow (BM). (C) The combination of DS and IM significantly decreases CML LSK frequency and reduces leukemia cells in various cell subsets in the mouse spleen. The analysis was carried out in cells collected at the end of the treatments. Con: control. (B and C) N=3, 4, and 4 for IM, DS, and IM+DS treatment groups; respectively. In the control group, n=5 for measuring CML cell numbers in various populations, and n=4 for determining protein levels by CyTOF mass cytometry.