Human NK cells display similar sensitivity to the CML microenvironment. (A) Heat map showing the expression of iNK-CML genes in NK cells across healthy donors and 3 CML prognostic groups. Figure created with http://scdbm.ddnetbio.com. (B) iNK-CML gene set module score is significantly enriched in group C patients' NK cells compared with healthy controls. Kruskal-Wallis test with Dunn multiple comparisons test. (C) CISH expression in NK cells across different prognostic groups. Kruskal-Wallis test with Dunn multiple comparisons test. (D) Top pathways enriched in group C NK cells compared with healthy controls identified by gene set enrichment analysis. (E) Target-specific degranulation in NK cells sorted from healthy or PBMCs from newly diagnosed patients with CML. Mann Whitney U test, mean ± SD. (F) The altered expression of CD27 (left) and CD11b (right) in peripheral blood NK cells from patients with CML. Mann Whitney U test, mean ± SD. (G) Target-specific NK cell degranulation in healthy NK cells preexposed to plasma samples of age-matched healthy donors or untreated chronic phase (CP) patients with CML. Median; Kruskal-Wallis test with Dunn multiple comparisons test. (H) K562 cell killing by healthy NK cells preconditioned with healthy plasma (green) or CML plasma (dark red). Mean ± SD; multiple unpaired t test. (I) Target-specific degranulation in CISH^KD (shaded) or scrambled-treated NK cells preexposed to healthy or CML CP plasma. Mean ± SD; 2-way ANOVA with Fisher's least significant difference test. (J) Degranulation in etanercept-treated (shaded) or untreated NK cells preexposed to healthy or CML CP plasma. Mean ± SD; 2-way ANOVA with Fisher's least significant difference test. For all experiments, ∗P ≤ .05; ∗∗P ≤ .01; ∗∗∗P ≤ .001; ∗∗∗∗P ≤ .0001; n = 3 to 9 individuals per group. HD, healthy donor; ns, nonsignificant; PBMCs, peripheral blood mononuclear cells.