While ibrutinib inhibits pro-survival signals in the lymph node microenvironment and causes leukemic cells to leave the tissue niches, venetoclax antagonizes Bcl-2 and activates mitochondrial apoptosis in the bloodstream, where CLL cells are deprived of the short-lived anti-apoptotic molecules (e.g., Mcl-1) [148]. Here, MCL1 is linked to B-cell chronic lymphocytic leukemia.