These included genes responsible for post-translational modification of Ras proteins—RCE1 and ICMT, genes in the MAPK signalling pathway—RAF1 and SHOC2 and a guanine nucleotide exchange factor (GEF) for the Rac GTPases named PREX1. Unlike the other identified hits, PREX1 was found to be essential only for Ras-driven AML, but not in the other cancer types that were tested, showing that synthetic interactions with oncogenes can be cell context-dependent. Here, PREX1 is linked to acute myeloid leukemia.