Indeed, this lack of HDMX-targeting hasbeen shown to limit the therapeutic efficacy of HDM2-targeting smallmolecules in tumor cells.25,52,53 This may be a particular problem in cases of DLBCL, which have alarge array of copy number alterations that decrease p53 activityand where overexpression of HDM2 and HDMX is common.24,28. The gene discussed is MDM4; the disease is diffuse large B-cell lymphoma.