Targeted therapy of acute myeloid leukemia in 2012: towards individualized therapy

Advances in molecular diagnostics in acute myeloid leukemia (AML) have translated into significant advances in our understanding of disease prognosis and biology, and the identification of new targets for therapy. The best described of these are mutations in Fms-like tyrosine kinase 3, nucleophosmin 1, and CCAAT enhancer-binding protein-alpha in those with cytogenetically AML, which allow more accurate risk stratification and help better 'target' patients who may benefit from allogeneic transplantation (specifically those with activating FLT3 mutation). Among the new targets identified for clinical trials are FLT3 mutation (a target for tyrosine kinase inhibitors), CD33 expression (a target of monoclonal antibodies and immunotoxins), aberrant methylation (target of hypomethylating agents), and overexpression of the chemokine receptor CXCR4 (a target for inhibition by small molecule or monoclonal antibody). We are advancing towards an era of personalized medicine in AML, and can now better identify specific patients who may benefit from specific therapies with less toxicity.