Fig. 7. EZH2 inhibitors increase CD38 and CD48 expression and enhance Dara-mediated ADCC.

a Schematic utilizing EZH2 inhibitor to balance the expression of CD38 and CD48 in KDM6A-KO MM cells. b, Western blot of CD38 and CD48 protein levels in KDM6A-KO and control H929 cells treated with Taze (5 μM) for 4 days. q-RT-PCR for CD38 (c) and CD48 (d) mRNA in KDM6A-KO and control H929 cells treated with Taze (5 μM) for 4 days. Data were normalized against GAPDH (mean ± SEM, n = 3 biologically independent experiments). ns, not significant; ***p < 0.001 (two-sided student’s t test). e Representative flow cytometry analysis of CD38 and CD48 expression in KDM6A WT and KO H929 cells treated with Taze (5 μM) for 4 days. H3K27me3 ChIP-qPCR analysis at the CD38 (f) and CD48 (g) genes in KDM6A WT and KO H929 cells (mean ± SEM, n = 3 biologically independent experiments). ***p < 0.001 (two-sided student’s t test). KDM6A WT and KO H929 cells were treated with Taze (5 μM) for 4 days, then co-cultured with primary human NK cells and Dara (h) or Isa (i) and subjected to ADCC assay (mean ± SEM, n = 3 biologically independent experiments). ns, not significant; **p < 0.01 (two-sided student’s t test). j KDM6A WT and KO H929 cells were treated with Taze (5 μM) for 4 days, and then co-cultured with Dara and primary NK cells for 6 hours. The supernatant was collected for granzyme B ELISA assay (mean ± SEM, n = 3 biologically independent experiments). **p < 0.01; ***p < 0.001 (two-sided student’s t test). k The patients’ MM cells were treated with DMSO or Taze (5 μM) for 4 days, followed by the addition of Dara and incubation for 12 hours. Cell cytotoxicity was assessed by flow cytometry. (n = 10 for each group). Box plots represent the median, 25th, and 75th percentiles, and whiskers represent the values of min and max. *p < 0.05 (two-sided paired student’s t test). Source data are provided as a Source Data file.