Overall, while the general strategy of inhibiting both RAF and MEK along the MAPK cascade appears to be promising even outside the clinically validated BRAF-mut genetic context (see also earlier work conducted by our group in leukemia models, [48]), the optimal selection of agents/mechanisms of action of RAF and MEK inhibitors to be combined remains to be addressed, taking into account the clinical tolerability profile of individual agents/combinations. This evidence concerns the gene RAF1 and leukemia.