In vivoinhibition of NAMPT results in reduced T-ALL burden in NSG mice owing to abrogated deacetylation of LMO2. (A) Xenotransplantation of NSG mice with either MOLT-4 cells, transduced with WT or K74/78R mutant LMO2-lentivirus, or primary T-ALL patient cells. Transplanted mice were injected intraperitoneally (i.p.) with 20 mg/kg of FK866 once a day for 2 (MOLT4 cells) or 3 (T-ALL patient cells) weeks. The same concentration of HGC was injected as a vehicle control. (B-D) Fold changes of percent of human CD45⁺ primary T-ALL patient cells (B) and Molt-4 cells (C-D) in bone marrow of FK866-treated mice to HGC group are shown. Data represent mean ± standard error of the mean (****P < .0001), n = 5 to 8 mice per group. (E-H) Duolink in situ PLAs of human CD45⁺ cells isolated from bone marrow of mice transplanted with primary T-ALL patient cells (E-F) or MOLT-4 cells (G-H). “WT” and “K74/78R” indicate mice transplanted with MOLT-4 cells transduced with WT or K74/48R LMO2 mutant, respectively. Cells were stained with anti-LMO2 and anti-acetylated lysine (E,G) or anti-LMO2 and anti-LDB1 antibodies (F,H). Representative images are shown. Scale bars: 10 μm. (I) mRNA expression levels of the indicated genes in human CD45⁺ cells isolated from bone marrow of xenotransplanted mice. mRNA expression was assessed using quantitative RT-PCR, and is expressed as arbitrary units (AUs). Target gene/GAPDH mRNA expression ratios are shown. Data show means ± SD from 5 independent experiments, each in triplicate (*P < .05).