The role of the proto-oncogene MYC as a driver of lymphoma has been known since the 1980s, but the mechanisms underlying its dysregulation are not completely understood. In this issue of Blood Cancer Discovery, Iyer and colleagues employ a CRISPR interference screen targeted at open chromatin regions to unveil enhancers critical for MYC overexpression in lymphoma, including a novel regulatory element in the MYC locus that controls germinal center reentry and is recurrently amplified in diffuse large B-cell lymphomas (germinal center B-cell diffuse large B-cell lymphoma).

See related article by Iyer et al., p. 233

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