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Bethany LaVergne and Curt Phifer, Ph.D. at Northwestern State University Fabiola Gomez, Ph.D. and Varsha Gandhi, Ph.D.; MD Anderson Cancer Center.

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Presentation on theme: "Bethany LaVergne and Curt Phifer, Ph.D. at Northwestern State University Fabiola Gomez, Ph.D. and Varsha Gandhi, Ph.D.; MD Anderson Cancer Center."— Presentation transcript:

1 Bethany LaVergne and Curt Phifer, Ph.D. at Northwestern State University Fabiola Gomez, Ph.D. and Varsha Gandhi, Ph.D.; MD Anderson Cancer Center

2  “A disease in which abnormal cells divide without control and can invade nearby tissues” (NCI dictionary)  Enhanced survival mechanisms  difficult to kill cancer cells  Physical, emotional, and financial impact  Prevention and treatment protocols for many cancers are available

3  Leukemia = cancer of the blood  Lymphocytic = B-lymphocytes  Chronic = slow, gradual development  Patients are 60-80 years old; rarely under 40  Complications with immune system  Family history is good predictor of risk  Elevated levels of Bcl- 2 and Pim kinase

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5  ABT- 737 (Abbot Labs) binds to and sequesters Bcl- 2  AZD- 1208 (Astra Zeneca) inhibits Pim kinase function

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7  Blood samples were obtained from 7 CLL patients and 1 healthy blood donor  Mononuclear cells (including B-lymphocytes) were isolated from blood  Each sample was treated 24 hours total  Cell death determined by Annexin V/Propidium iodide staining  Additive, Antagonistic, and Synergistic

8  1 nm was used in combination treatments  3 μM and 10 μM AZD- 1208 were determined sufficient by a similar experiment

9 1 nM ABT- 737 3 μM AZD- 1208 10 μM AZD- 1208 1 nM ABT- 737 + 3 μM AZD- 1208 1 nM ABT- 737 + 10 μM AZD- 1208

10 1 nM ABT- 737 3 μM AZD- 1208 10 μM AZD- 1208 1 nM ABT- 737 + 3 μM AZD- 1208 1 nM ABT- 737 + 10 μM AZD- 1208 No treatment DMSO

11  Variation between samples  Additive results at best  Highest % cell death induced: 40% from 1 nM ABT- 737 + 10 μM AZD- 1208

12 Kang, M, Reynolds, C. “Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy.” Clinical Cancer Research 2009, 15: 1126-1132. Martinou, J, Youle, R. “Mitochondria in Apoptosis: Bcl-2 Family Members and Mitochondrial Dynamics.” Developmental Cell 2011, 21: 92-101. Nawijn, M, Alendar, A. Berns, A. For better or for worse: the role of Pim oncogenes in tumorigenesis. Nature Reviews 2011, 72: 23-34. Perez, K, Winer, E. “Chronic Lymphocytic Leukemia: Something Old, Something New and Something Borrowed…” Rhode Island Medicine and Health 2011, 94: 15- 18. Reed, J, Pellecchia, M. Apoptosis-based therapies for hematologic malignancies. Blood 2005, 106: 408-416. Song, J, Kraft, A. Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737. Cancer Research 2012, 72: 294-303.


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