BH3 profiling and other preclinical methods have identified a number of high-risk leukemias, including early T cell precursor ALL [44], immature T-ALL [45], KMT2A (MLL)-rearranged ALL [46,47] and Philadelphia chromosome-positive ALL [48,49] as well as TCF-HLF-positive ALL, the most aggressive form of ALL [50], all of which are Bcl-2 dependent and sensitive in vitro and in vivo to treatment with venetoclax. This evidence concerns the gene HLF and acute lymphoblastic leukemia.