NK cells with a less cytotoxic CD56^bright molecular signature are expanded in B/T-ALL. (A) Schematic diagram depicting the steps to estimate the relative proportions of CD56^bright NK cells and CD56^dim NK cells in healthy donors (GSE13159, GSE65136), in patients with B/T-ALL from the MILE study (GSE13159), and in patients with B-ALL from the COG P9906 clinical trial (GSE11877) using CIBERSORT. Using GSE21774, which contains the transcriptomic profile of CD56^bright and CD56^dim NK cell subsets as the reference file, we deconvoluted the bulk transcriptomic profiles of healthy donors, MILE patients with B/T-ALL, and COG P9906 patients with B-ALL. (B) Comparison of CD56^bright NK cell and CD56^dim NK cell frequencies in BMMCs from healthy donors (blue; n = 74), MILE patients with B-ALL (olive; n = 540), MILE patients with T-ALL (green; n = 170), and B-ALL COG P9906 patients (red; n = 131) (upper panel) and in PBMCs from healthy donors (blue; n = 20), MILE patients with B-ALL (olive; n = 36), T-ALL MILE patients (green; n = 4), and B-ALL COG P9906 patients (red; n = 76) (lower panel). Data are median ± interquartile range. Frequencies (C) and representative dot plots (D) of CD56^brightCD27⁺, CD56^brightCD27⁻, CD56^dimCD27⁺, and CD56^dimCD27⁻ NK cell subsets defined by CyTOF analysis of BMMCs from healthy donors (n = 12) and B/T-ALL patients (n = 12). Frequencies (E) and representative dot plots (F) of CD56^brightCD27⁺, CD56^brightCD27⁻, CD56^dimCD27⁺, and CD56^dimCD27⁻ NK cell subsets defined by CyTOF analysis of PBMCs from healthy donors (n = 10) and patients with B/T-ALL (n = 8). Data are mean ± standard error of the mean for each subset. Exact P values were calculated using the Mann-Whitney U test. ns, nonsignificant.