Identification and characterization of novel oncogenes in chronic eosinophilic leukemia and T-cell acute lymphoblastic leukemia.
Research conducted in my group in the period 2006-2009 has led to a better understanding of the oncogenic mechanisms of the FIP1L1-PDGFRA and NUP214-ABL1 oncogenes. Insights into these mechanisms may help us to design novel strategies to treat leukemia. In addition, we have identified the small molecule inhibitor sorafenib as a potent inhibitor of the FIP1L1-PDGFRA and its T674I imatinib resistant mutant. Sorafenib was originally developed as a BRAF inhibitor, but our work demonstrates that sorafenib can also be used to treat FIP1L1-PDGFRA positive leukemia, demonstrating that new therapies to treat rare leukemias may be simply found by testing drugs that are already in use for the treatment of other diseases. Finally, using genome-wide screening approaches, we have identified the MYB gene as a novel oncogene implicated in the pathogenesis of T-ALL, and we suggest that MYB may represent a novel target for therapy in T-ALL as well as in other cancers.
Cools
J
J
Center for Human Genetics, Faculty of Medicine, K.U.Leuven, Department of Molecular and Developmental Genetics, VIB - Gasthuisberg O&N1, Herestraat 49 - B 3000 Leuven.
D001557:Benzenesulfonates / Q000627:therapeutic use; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000235:genetics* / Q000628:therapy; D009536:Niacinamide / Q000031:analogs & derivatives; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D010671:Phenylurea Compounds; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics*; D000077157:Sorafenib; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
D001557:Benzenesulfonates; C085914:NUP214 protein, human; D028861:Nuclear Pore Complex Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D039221:mRNA Cleavage and Polyadenylation Factors; D009536:Niacinamide; D000077157:Sorafenib; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha