1. Finding Cancer Genes

24. 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)

25. Finding Cancer Genes 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.

26. Finding Cancer Genes 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.

27. Finding Cancer Genes

32. Bcr-Abl

33. Non-physiological Activation of Bcr-Abl Activation of Signaling

34. c-Abl – Physiological Roles c-Abl is a nuclear-shuttling protein that regulates p53

35. c-Abl – Physiological Roles

36. c-Abl Kinase Domain Structure

37. STI-571

39. www.cmlsupport.com

48. Parametric Linkage analysis

52. 3

57. Fig. 1. The β-catenin protein interaction network. Michael B. Major et al. Science 2007;316:1043-1046 Published by AAAS

58. Fig. 3. WTX promotes β-catenin ubiquitination and degradation. Michael B. Major et al. Science 2007;316:1043-1046 Published by AAAS

62. Tumour Suppressors Example 4: REST

67. Thomas F. Westbrook, Eric S. Martin, Michael R. Schlabach, Yumei Leng, Anthony C. Liang, Bin Feng, Jean J.... A Genetic Screen for Candidate Tumor Suppressors Identifies REST Cell, Volume 121, Issue 6, 2005, 837 - 848