Molecular therapeutic approaches to acute myeloid leukemia: targeting aberrant chromatin dynamics and signal transduction

Acute myeloid leukemia research and clinical management have greatly benefited from the achievements in molecular biology regarding the identification of the underlying pathogenetic mechanisms of transformation and resistance to therapy. In particular, two categories of alterations, the aberrant activity of transcription/chromatin-remodeling factors and the deregulated activation of signal transduction pathways, have been demonstrated to play a pivotal role in leukemic cell differentiation, proliferation and resistance to apoptosis. These molecular lesions have proven to be suitable therapeutic targets in acute promyelocytic leukemia and chronic myeloid leukemia and are now also seen as therapeutic targets for a wider group of leukemic disorders. The development of novel drugs such as histone deacetylase inhibitors, demethylating agents and inhibitors of receptor tyrosine kinases may potentially benefit acute myeloid leukemia patients.