Here we explore the regulatory role of PHD3 on HIF2α expression and its impact on hypoxia-mediated apoptosis in MM cells and demonstrate that restoring PHD3 expression using a lentivirus vector or treating MM cells with a demethyltransferase inhibitor rescues O2-dependent regulation of HIF2α in MM cells and that this is sufficient to sensitize MM cells to hypoxia-mediated apoptosis in vitro. The gene discussed is EPAS1; the disease is Miyoshi myopathy.