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Understanding the molecular mechanisms underlying treatment failure in chronic diseases such as leukaemia is an essential biological question with important clinical impact. In the last years, we have performed high throughput characterization of the enhancer landscape in Chronic Lymphocytic Leukaemia upon BTK inhibitory treatment aiming at shedding lights into Ibrutinib-treatment resistance mechanisms beyond the well-described mutations. Next, our lab research mission is to: i) investigate the role of key enhancers and transcription factors as major modulators of the transcriptional landscape in immune cells ii) defining the molecular and epigenomic feature of normal, autoimmune and. malignant B -cell of diverse maturation status in the presence of 1st and 2nd generation targeted therapeutic agents.