Naval Daver and Paresh Vyas discuss mechanisms of resistance to targeted therapies in AML, including the impact of small clones and non-cell intrinsic effects. They explore the modulation of leukemia by therapies and the potential of using companion diagnostics and immunotherapies to predict long-term responders. The podcast also highlights the importance of testing for flip three mutation in AML patients and the role of epigenetic targets in therapy resistance.