Although venetoclax has potent antileukemic efficacy, resistance can occur due to its inability to inhibit MCL-1, which is stabilized by the MAPK pathway106.The RAS/BRAF/MAPK/ERK cascade is activated by mutations in novel CLL drivers, such as NRAS, KRAS, BRAF, PTPN11, and MAP2K1/2 (MEK1/2)107. Here, MAP2K1 is linked to B-cell chronic lymphocytic leukemia.