In addition to retrotransposon alterations, our integrated analysis of ATAC-seq and RNA-seq further reveals a potential link between GNAS KO plus HDAC3 inhibition and the ETS family transcription factors PU.1 and SpiB for transcriptional regulation of IFN signal activation in B-cell lymphoma. Here, HDAC3 is linked to B-cell non-Hodgkin lymphoma.