JAK inhibitors reduce engraftment of primary human AML but not normal stem cells in NSG mice. (A) Human primary AML and cord blood MNCs were treated with AZD1480 or DMSO for 72 hours and transplanted into sublethally irradiated NSG mice. After 8 weeks, BM cells were analyzed for expression of human CD45+ cells. (B) Human CD45+ cell engraftment for AZD1480 (0.1 μM)-treated and control DMSO-treated cells from 3 different AML samples (AML090, n = 5 mice per group; AML532, n = 3-4 mice per group; AML 593, n = 4 mice per group). The baseline levels of pSTAT3/5 in each AML sample are shown in the figure. (C) Representative fluorescence-activated cell sorter plot of human AML CD45+ cell engraftment in BM. (D) Expression of differentiation markers on human AML CD45+ cells engrafted in BM. (E) Engraftment of human cord blood CD45+ cells exposed to AZD1480 (0.5 µM) or DMSO for 72 hours in NSG mice 8 weeks after transplant (2 different samples, n = 4 for each group per sample). (F) Representative fluorescence-activated cell sorter plot of human CB CD45+ cell engraftment in BM. (G) Expression of differentiation markers on human CB CD45+ cell engrafted in BM. (H) Human CD45+ cell engraftment for INC424 (0.1 μM)-treated and control DMSO-treated AML cells (AML442, n = 8 mice per group; MCF pSTAT3 = 16, MCF pSTAT5 = 22.8). (I) Expression of differentiation markers on human AML CD45+ cells engrafted in BM.