PRMT1 inhibition enhances elimination of MLL-r ALL cells by TKI treatment. (A) Western blotting of indicated total and phospho-proteins in primary MLL-r ALL cells treated with vehicle, MS023, PKC412, or an MS023/PKC412 combination. (B) Cell viability of MLL-r ALL samples (n = 6) treated with vehicle, MS023, PKC412, or MS023/PKC412. (C) Apoptosis of MLL-r ALL samples (n = 6) treated with PKC412 or MS023/PKC412. (D) Apoptosis of shCtrl- or shPRMT1-transduced SEM cells treated with vehicle or PKC412. (E) Experimental design. To assess MS023 effects in vivo, we transplanted primary MLL-r ALL cells into NSG mice. After the engraftment of human cells reached 1%, mice were treated with vehicle, PKC412, MS023, or a combination for 4 weeks. Posttreatment, engrafted human cells were analyzed. Secondary transplantation was then performed. Percentage of human CD45⁺/CD19⁺ cells engrafted in BM (F), SP (G), and PB (H) of recipient NSG mice transplanted with #5 or #6 primary MLL-r ALL cells. Mice with patient-derived xenografts were treated as indicated in each panel for 4 weeks. Percentage of human CD45⁺/CD19⁺ cells engrafted in BM (I), SP (J), and PB (K) of secondary recipient NSG mice receiving primary donor cells (#5) from mice treated as indicated in each panel. (L) Survival of NSG mice engrafted with primary MLL-r ALL cells treated with vehicle, PKC412, MS023, or PKC412/MS023. Error bars represent standard error of the mean. *P < .05; **P < .01; ***P < .001; ****P < .0001.