Increasing understanding of AML biology is leading to an increasing number of targeted therapies directed at underlying molecular abnormalities.Due to the central regulatory role of signal transduction pathways, many of these targeted therapies are directed against key signal transduction proteins.Multi-parameter flow cytometry assessing phosphorylatedproteins coupled with immunophenotyping is playing a key role in this setting as well as abnormalities in these proteins,and in signaling responses, potentially serving a useful diagnostic role in identification of abnormal cells particularly in minimal residual disease and post-therapy.