Loss of STAT3 leads to an accelerated AML progression and aggressive liver infiltration. (A) Analysis of the Beat AML cohorts shows STAT3 gene expression in patients harboring common AML-driver mutations (n = 286). (B) AML cells were lentivirally transduced using the lentiCRISPR v2 plasmid, encoding a puromycin resistance gene, the Cas9 endonuclease, and sgRNA targeting STAT3 or a nontargeting control sgRNA. Confirmed single-cell clones were intravenously transplanted into immunocompromised NSG mice. Transplanted recipient mice have been euthanized as soon as they exhibited clinical signs of leukemia and organs were processed for further analysis. (C) Kaplan-Meier plot of mice receiving STAT3^KO THP-1 (n = 18), MOLM-13 (n = 8) or HEL (n = 8) cells compared to mice transplanted with wildtype STAT3 cells (n = 18). (D) Percentage of hCD45⁺ AML cells isolated from the bone marrow (THP-1, n = 18; MOLM-13, n = 8; HEL, n = 8). (E) Representative hematoxylin and eosin-stained liver sections of diseased mice receiving THP-1 cells at the time of euthanasia. (F) hCD45⁺ cells isolated from the liver of diseased animals (THP-1, n = 18; MOLM-13, n = 8; HEL, n = 8). Log-rank (Mantel-Cox) test was performed to analyze the survival difference between the 2 groups. Further statistical analysis was performed using Student t test. P values <.05 were considered statistically significant. ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. Error bars represent mean ± standard deviation. KO, knockout; WT, wildtype.