Furthermore, the HMGB1/RAGE axis not only activates ERK to inhibit mTOR and induce autophagy but also activates NF-κB to upregulate drug efflux pumps like P-glycoprotein (P-gp) and MRP, creating a multi-faceted defense system against chemotherapeutic agents in acute leukemia [95] (Figure 2). This evidence concerns the gene HMGB1 and acute leukemia.