ATRA drives CD38 upregulation with limited additional cellular impact, whereas Aza leads to a broad interferon-mediated response. (A) Integrated mRNA-seq (n = 2 per drug treatment) and cell surface proteomics (n = 2 per drug treatment) across RPMI-8226 treatment with 10 nM ATRA, 2 μM Aza, and 10 nM panobinostat (Pano). All plots are in comparison with control replicates treated with 0.1% DMSO. Doses chosen are based on those previously published to lead to CD38 upregulation for each agent. Data points shown are for proteins and genes corresponding to Uniprot-annotated membrane-spanning proteins. Log₂ fold-change cutoffs shown at |0.5| for ATRA and |2.0| for Aza and Pano to increase clarity of plots given many fewer changed genes with ATRA treatment. (B) RNA-seq for same samples with ATRA or Aza treatment vs DMSO but here showing all mapped genes, not just those annotated as membrane-spanning. Significance cutoff at P value <.05 with log₂ fold-change cutoff set at |0.8| to illustrate prominent differences above this level in transcriptome alteration after either ATRA or Aza treatment. (C) KEGG analysis of genes from RNA-seq data set meeting cutoff criteria of P value <.05 and log₂ fold-change >0.8 after Aza treatment. DMSO, dimethyl sulfoxide.