Overcoming Acquired Epigenetic Resistance to BTK Inhibitors

We modeled the development of resistance to the BTK inhibitor ibrutinib in the ABC subtype of diffuse large B cell lymphoma (DLBCL), which relies on chronic active BCR signaling for survival. The primary mode of resistance was epigenetic, driven in part by the transcription factor TCF4. We identified clinically available drugs that can treat epigenetic ibrutinib resistance, suggesting combination therapeutic strategies. SRA archive contains NGS datasets supporting this project. More detailed information regarding raw NGS datasets can also be found at https://lymphochip.nih.gov/local/Staudt_Ibrutinib_resistance_BCD/