Effects of cholesterol regulation by SOX9-DHCR24 axis in DLBCL. (A) Aggressive DLBCLs harboring the IGH-BCL2 translocation overexpress SOX9, which in turn activates the DHCR24, leading to cholesterol synthesis. Increased cellular cholesterol levels regulate DLBCL cell survival and proliferation. (B) The blockade of SOX9-DHCR24 axis by short hairpin-SOX9 RNA, specific SOX9 inhibitors, or simvastatin inhibits cholesterol synthesis, reduces cellular cholesterol levels, ultimately mediating DLBCL apoptotic cell death both in vitro and in vivo. This axis could be exploited in combination with DLBCL-specific therapy to treat patients affected by advanced forms of DLBCL overexpressing SOX9.