2. Bcl-2 family is compose of anti-apoptotic and pro-apoptotic proteins that play an important role is cell death regulation.

3. The Intrinsic apoptotic pathway in C. elegans and mammalian Cells have many similarities.

4. Intrinsic Apoptotic Pathway

6. Follicular Lymphoma Identified as a proliferation of malignant germinal center B cells. Caused in 20-30% of patients by t(14;18) translocation. Symptoms: – Enlargement of the lymph nodes in the neck, underarm, and stomach. – Shortness of breath – Fatigue Identified by fluorescence in situ hybridization in 85% of all causes.

7. Follicular lymphoma progression consist of different genetic hits

8. BCL-2 overexpression on its own is not highly oncogenic. Progression to malignancy requires synergistic mutations with myc or other form of mutations.

9. Reference Kridel R, Sehn H. L, Gascoyne D. R. (2012) Pathogenesis of follicular lymphoma. J Clin Invest 122(10):3424-3431. doi:10.1172/JCI63186 Cory S, Huang C. S. D, Adams M. J. The Bcl-2 family: Roles in cell survival and oncogenesis. Oncogene (2003) 22, 8590- 8607. doi:10.1038/sj.onc.1207102. Lymphoma Research Foundation. (2012 )Follicular Lymphoma. http://www.lymphoma.org/site/pp.asp?c=bkLTKaOQLmK8E&b=63001555 Willis S, Day L. C, Hinds G. M, Huang C. S. D. (2003) The Bcl-2 Regulated Apoptotic Pathway. Journal of Cell Science. 116, 4053-4056. doi:10.1242/jcs.00754 Brunelle, J. K., Letai, A. (2009). Control of Mitochondria Apoptosis by the Bcl-2 family. Journal of Cell Science, 122(4); 437-441. doi:10.1242/jcs.031682 MacManus, P. J., Linnik, D. M. (1997). Gene Expression Induced by Cerebral Ischemia: An Apoptotic Perspective. Journal of Cerebral Blood Flow & Metabolism, 17, 815-832. doi:10.1038/aj.jcbfm.9590266 Lessene, G., Czabotar E. P., Colman M. P. (2008). BCL-2 family antagonists for cancer therapy. Nature Reviews Drug Discovery, 7, 989-1000. doi:10.1038/nrd2658 Degterev, A., Yuan, J. (2008). Expansion and evolution of cell death programmes. Nature Reviews Molecular Cell Biology, 9, 378-390. doi:10.1038/nrm2393 Youle, J. R, Strasser A. (2008). The BCL-2 protein family: Opposing activities that mediate cell death. Nature Reviews Molecular Cell Biology, 9, 47-59. doi:10.1038/nrm2308 From Mendel to the Human Genome Project. (2013). Cancer Genetics. Web. http://www.discoveryandinnovation.com/BIOL202/notes/lecture20.html Yasuda I., Goto N., Tsurumi H., Nakashima M., Doi S., Iwashita T. (2012). Endoscopic Ultrasound-Guided Fine Needle Aspiration Biopsy for Diagnosis of Lymphoproliferative Disorders: Feasiability of Immunohistological, Flow Cytometric, and Cytogenetic Assessments. The American Journal of Gastroenterology, 107, 397-404. doi:10.1038/ajg.2011.350 Weinberg, R. (2014). P53 and Apoptosis: Master Guardian and Executioner. In The Biology of Cancer (Second ed., p. 364). New York: Garland Science, Taylor & Francis Group.