What we will review this lecture: Receptor Tyrosine Kinase signalling: PI3K Pathway AKT, PDK1, PTEN RTK Signalling in Cancer Historical description of BCR-ABL Friedrich Grimminger, Ralph T. Schermuly & Hossein A. Ghofrani. Nature Reviews Drug Discovery 9, CML: Chronic Myelogenous Leukemia Asymptomatic at time of diagnosis Abnormal white blood cell count Stable for 3 5 years followed by Blast Crisis Fatal within 3 6 months of Blast crisis 20% of all leukemia's 5000 cases per year in US (compare with 180,000 lung cancer cases) CML: Chronic Myelogenous Leukemia All CML cells harbor Philadelphia chromosome 1960: Peter Nowell David Hungerford Nowell P, Hungerford D. "A minute chromosome in chronic granulocytic leukemia." Science 1960;132:1497. 1973: Janet D. Rowley Discovered t(9;22) Rowley JD. "A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining [letter]". Nature 1973;243:2903. c-Abl Kinase Domain Structure STI-571