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Cancer Genetics Myc over-expression – t(8;14) translocation Another paradigm: Altered regulation of tyrosine kinases
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Cancer Genetics 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)
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Cancer Genetics 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.
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Cancer Genetics 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;243:290–3.
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Cancer Genetics
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Bcr-Abl
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Non-physiological Activation of Bcr-Abl Activation of Signaling
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c-Abl – Physiological Roles c-Abl is a nuclear-shuttling protein that regulates p53
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c-Abl – Physiological Roles
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Kinase activity of c-Abl required for: – Transformation (in Bcr-Abl context) – Regulation of p53
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c-Abl Kinase Domain Structure
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STI-571
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www.cmlsupport.com
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STI-571 Patients with Ph+ CML treated with STI-571 had estimated overall survival rates of 91% in late chronic phase, 66% in accelerated phase, and 18% in blast crisis 2 years after initiating treatment.
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HER2/ErbB2 and Breast Cancer
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HER2/ErbB2 Therapeutics
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Parametric Linkage analysis
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