Here, we showed that coculture with MSCs enabled T-ALL cells to resist chemotherapeutic cytotoxicity, and reported for the first time that this was associated with mitochondrial ROS levels decrease, pro-glycolytic phenotype switching and mitochondrial fragmentation, all of which were triggered by extracellular signal-regulated kinase (ERK) activation-induced dynamin-related protein 1 (Drp1) phosphorylation. The gene discussed is DNM1L; the disease is acute lymphoblastic leukemia.