Researchers at the Unversity of Texas M.D. Anderson Cancer Center have found a drug which appears highly effective in destroying human acute myeloid leukemia (AML) in cell cultures. M. Konopleva et al. published the results of their studies in the November 15th issue of Cancer Cell. The drug is a small molecule mimetic, ABT-737, which was designed to bind to the anti-apoptotic protein, Bcl-2. The investigators demonstrated that ABT-737 disrupts the Bcl-2/Bax complex as well as activates the Bak-dependent and Bim-independent intrinsic apoptotic pathway. In previous pre-clinical studies, ABT-737 also was found to have anti-tumor activity against lymphoma and small-cell lung cancers. The scientists reported that "ABT-737 can effectively kill AML blast, progenitor, and stem cells without affecting the hematopoietic (stem) cells." However, it was also reported that certain subpopulation(s) of the AML cells were resistant to ABT-737. These drug resistant cells were found to overexpress another anti-apoptotic protein in the Bcl-2 family, Mcl-1. With a MAP-kinase (MAPK) inhibitor, Mcl-1 expression was knocked down in the leukemic cells. A combination of the two agents, ABT-737 and MAPK inhibitor, destroyed all the AML cells in vitro. It was further noted that targeting Mcl-1 may be of greater importance than Bcl-2 since patients whose cells overexpress Mcl-1 have a poorer outcome. The authors concluded that drugs such ABT-737 could be a highly effective anti-leukemia agent since they are killing the progenitor and stem cells which are the cells responsible for AML.