To our knowledge, this investigation is the first to demonstrate that the SREBF2-cholesterol biosynthesis pathway is transcriptionally regulated by WNT/β-catenin, and that the SREBF2-cholesterol pathway is pivotal to the survival of murine Lck-Dlx5;Lck-MyrAkt2 lymphoma cells as well as a subset of human T-ALL cells. Here, LCK is linked to acute lymphoblastic leukemia.