Since there are at least four different types of opioid receptors and the precise mechanism through which D,L-methadone induces ALL cell apoptosis was not known, we previously investigated these issues and demonstrated that D,L-methadone-induced ALL apoptosis occurred via the μ-opioid receptor 1 (OPRM1), triggering ER Ca2+ release and decreased Ca2+ efflux, elevating [Ca2+]i that upregulated the calpain-1-Bid-cytochrome C-caspase-3/12 apoptotic pathway (Lee et al., 2021): OPRM1-↑[Ca2+]i-calpain-1-Bid-cyt C-caspase-3/12 pathway. The gene discussed is CYCS; the disease is acute lymphoblastic leukemia.