Immature JMML cells are susceptible to lysis by NK cells. (A) Expanded NK cells from 3 HDs were preincubated with spleen MNCs from patients with JMML or cord blood MNCs. NK cell effect on growth of CFUs was tested. Either 250 000 JMML or cord blood MNCs were incubated with 125 000 NK cells for 4 hours and then seeded into MethoCult with growth factors. CFUs were counted on day 12. Data were normalized to CFU numbers obtained in untreated control plates. The experiment was performed twice, with both data sets shown. (B) Expanded NK cells from 3 healthy donors were cocultured with JMML splenocytes (n = 2 patient samples), AML cells, or allogeneic healthy donor PBMCs. After 48 hours, cells were examined by mass cytometry. Cells were classified in clusters based on immune cell phenotype, and subpopulations then were evaluated to compare effects of NK cell–mediated lysis on different subpopulations. (C) Percent of total cells for the bulk, progenitor, and stem populations comparing JMML splenocytes cultured alone vs with NK cells are plotted, with asterisks denoting significant decreases in population size after coculture (P < .05).