Abstract: MYC is an oncogenic transcription factor which is overexpressed in up to 70% of cancers. High MYC levels promote cancer cell proliferation, metabolism and invasion. Despite decades of research, still therapeutic targeting of MYC remains a challenge. In this lecture I will describe the mechanisms through which MYC is overexpressed in cancer cells and discuss various strategies to target MYC. I will present our input in this field in case of hematologic malignancies: Burkitt lymphoma (BL) and chronic myelogenous leukemia (CML). We applied two strategies: 1) to target upstream regulators of MYC, namely IGH enhancers which boost MYC expression due to translocation in BL; 2) to identify essential downstream target genes of MYC in BL and CML.