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.
Piazza
Francesco
F
Padova University School of Medicine, Venetian Institute of Molecular Medicine, Unit of Hematological Malignancies, via Orus 2 35129 Padova, Italy. francesco.piazza@unipd.it
Semenzato
Gianpietro
G
D000208:Acute Disease; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002869:Chromosome Aberrations / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008967:Molecular Biology; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors