NK cell abundance and phenotype gradually revert upon BCR-ABL loss. (A) Schematic of BCR-ABL reversion experiment. After acquiring CML, mice were treated with tetracycline water and analyzed at different posttreatment time points. (B) Simple linear regression analysis showing a negative correlation between bone marrow NK cell frequencies of total CD45.1⁺ cells (y-axis) and CML burden defined as frequencies of CD45.2 Gr1⁺CD11b⁺ cells of total hematopoietic cells in the bone marrow (x-axis). (C) NK cell frequencies and absolute counts in control and CML mice at the diseased stage and 6 and 11 weeks after silencing the oncogene. (D) Restoration of maturation upon reverting CML. (E-H) Restoration of KLRG1 (E), NKp46 (F), inhibitory receptors (G), and Ki-67 (H) expression in NK cells during tetracycline treatment. (I) NK cell frequencies in total host cells in the spleen and blood of control, vehicle-treated CML, and 3-week post-TKI CML mice. (J) The expression of inhibitory receptors NKG2A (left), Lag-3, and TIGIT (right) in host NK cells derived from control, vehicle-treated CML, and TKI-treated CML mice. For all experiments, mean ± SD was plotted. One-way analysis of variance (ANOVA) with Dunnett post-hoc correction, ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001; ∗∗∗∗P ≤ .0001; n = 3 to 14 mice per group. Lag-3, lymphocyte activation gene 3; ns, non-significant; TIGIT, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains.