It is now accepted that FLT3 mutations in de novo AML are generally polyclonal; hence broader multi-kinase FLT3 inhibitors such as midostaurin and sorafenib have higher efficacy compared to relapsed AML where a FLT3 subclone gains selective advantage and responds better to more selective inhibitors such as gilteritinib and quizartinib [64]. Here, FLT3 is linked to acute myeloid leukemia.