Molecular Pathways: BCR-ABL
Cet article passe en revue les travaux récents sur les anomalies d'activation de diverses voies de signalisation par l'oncoprotéine BCR-ABL
Aberrant Tyrosine kinase (TK) activity is critical in many hematological disorders, including chronic myeloid leukemia (CML) characterized by the constitutive activity of BCR-ABL. ABL therefore represented a crucial target for new therapeutic strategies. The molecular pathways abnormally activated by the oncoprotein are summarized and they may represent additional opportunities to develop new drugs to overcome the resistance to TK inhibitors. Among them the PI3K/Akt pathway can be effectively blocked by mTOR inhibitors, or RAS pathway, resulting MEK1/2 and MAPK activation can be targeted. Furthermore, mitotic kinases can be blocked by Aurora kinase inhibitors or Pim kinases by selective serine-threonine kinase inhibitors. Finally, the abnormal pathways sustaining the self renewal of leukemic stem cells are described as possible targets to completely eradicate the leukemic clone including Hedgehog pathway which can be blocked by Smo inhibitors and CXCR4/SDF1 axis which can be targeted by specific antagonists.