Receptor Tyrosine Kinase And Downstream Signaling Pathways

Members of the RTK-RAS signaling pathway, including receptor tyrosine kinases (RTKs) such as FLT3, FMS, KIT, and VEGFR, and the NRAS and KRAS genes, are frequently (in more than 50% of patients) mutated in AML; as a result, this pathway appears to play a central role in leukemogenesis. The identification of these specific molecular alterations has not only helped in elucidating the mechanisms involved in leukemogen-esis, but also has resulted in targeted therapies, such as FLT3 inhibitors for AML patients with FLT3 ITD or FLT3 overexpression, RTK inhibitors for patients with KIT mutations or overexpression, as well as RAS inhibitors including farnesyltransferase inhibitors.51

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