RAS mutations are frequent events in AML, with their report- ed frequency being up to 30%.

7,8 Most mutations are point mutations involving codons 12, 13 and 61, with the N-RAS gene being mutated most frequently in hematopoeitic malignancy.9 In this study, the incorporation of RAS and RTK mutational analysis has increased the class I mutational rate to nearly 70%, the highest frequency reported for any AML subclass. Interestingly, class I mutations tended to be mutually exclusive, with only four cases possessing both a RAS and a RTK mutation. In conclusion, we believe that the above findings in patients with AML and inv(16) further support the two-hit model of leukemogenesis. In the future, it will be possible to confirm the relevance of such interactions using animal models, as has already been reported for FLT3-ITD and PML/RARα. 10 These results open up the possibility of incorporating targeted therapy for high risk patients with AML and inv(16), since specific inhibitors to activate RAS and RTK are already being employed in clinical trials.