Prevention of Leukemic Stem Cells Developing from Hematopoeic Stem Cells by Targetting the Ras/Raf

Prevention of Leukemic Stem Cells Developing from Hematopoeic Stem Cells by Targetting the Ras/Raf

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PROJECT TITLE: Prevention of Leukemic Stem Cells developing from Hematopoietic Stem Cells by targeting the Ras/Raf/MEK/ERK pathways
INVESTIGATOR: Michelle Nguyen (Spring 2014)
PROJECT SUMMARY: According to the study done in 2014 by the National Cancer Institute, leukemia is the 11th most common type of cancer (Howlader et al., 2011). This cancer that originate in the bone marrow or other tissues that form blood cells causing them to divide rapidly without any control (Wu, 2012). These leukemia stem cells are derived from hematopoietic stem cells but because of high telomerase activity, the stem cells have the ability to self-renew limitlessly (Heidel, Mar, & Armstrong, 2011). As of right now, there are many treatments available such as chemotherapy, biological therapy, targeted therapy, and radiation therapy. But the most promising form of treatment with those is stem cell transplant, which is used in joint with the other therapies. The preexisting leukemia stem cells are first targeted and destroyed before implanting healthy hematopoietic stem cells. These cells will then proliferated and differentiate into white blood cells, used in immune response (Wang & Dick, 2005).
In previous studies, there is evidence that suggests that the proliferation, differentiation, and prevention of apoptosis of hematopoietic stem cells stems from the Ras/Raf/MEK/ERK pathways being active (Montagut & Settleman, 2009). This particular pathways has been associated with most cancers but for prostate cancer, it would be more advantageous to induce the pathway whereas, for blood cancers, the more ideal approach would be to inhibit these pathways. Because these pathways are important for normal cellular activity and should be inhibited selectively for leu...


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...ntagut, C., & Settleman, J. (2009). Targeting the RAF-MEK-ERK pathway in cancer therapy. Cancer Letters. doi:10.1016/j.canlet.2009.01.022
Siegel, R., Naishadham, D., & Jemal, A. (2013). Cancer Statistics, 2013. CA Cancer J Clin, 63, 11–30. doi:10.3322/caac.21166.
Stepulak, A., Sifringer, M., Rzeski, W., Endesfelder, S., Gratopp, A., Pohl, E. E., … Ikonomidou, C. (2005). NMDA antagonist inhibits the extracellular signal-regulated kinase pathway and suppresses cancer growth. Proceedings of the National Academy of Sciences of the United States of America, 102, 15605–15610. doi:10.1073/pnas.0507679102
Wang, J. C. Y., & Dick, J. E. (2005). Cancer stem cells: lessons from leukemia. Trends in Cell Biology, 15, 494–501. doi:10.1016/j.tcb.2005.07.004
Wu, L. (2012). Leukemias. Medscape. Retrieved February 14, 2014, from http://emedicine.medscape.com/article/1201870-overview



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