Effects of cigarette smoke exposure in patients and mouse models with FLT3-mutant AML. (A) Table with response rates of patients shown in Figure 1B. Values are n (%). χ² test analysis was used for categorical variables. (B) Overall survival curve of patients (from panel A) (P = .0092). (C) Schematic representation of SE and AML introduction timeline for mouse modeling of smoking. (D) Representative MOLM13-luc bearing mice 3 days after being NS or SE. (E) Bioluminescent flux shown of MOLM13 bearing mice (n = 15 for NS and n = 30 for SE mice). (F) Leukemic burden of MOLM14-bearing mice 3, 10, and 24 days after injection (n = 7 mice per group for days 3 and 10; n = 5 for NS; and n = 4 for SE on day 24). (G) Representative mice exposed to NS or SE bearing the MV411-luc cells after days 5, 9, or 16 of engraftment. (n = 4 per group). (H) Cotinine levels in urine from NS or SE mice in ng/mL (n = 4). (I) Table with the top hypermethylated and hypomethylated genes from SE in AML cells from mouse spleens as compared with NS mice. (J) The Cancer Genome Atlas (TCGA) data from NEJM 2013 study.⁶ Patients with quartile of high or low Gata2 methylation survival depicted. ∗P < .05; ∗∗P < .01; ∗∗∗P < .001; ∗∗∗∗P < .0001. CR, complete remission; CRi, complete remission with incomplete count recovery; FLT3i, FLT3 inhibitor; HI, hematologic improvement; N, number; ORR, overall response rate; PR, partial response.