This web page was produced as an assignment for Gen677 at UW-Madison Spring 2010
Recent study reveals possible new
cure for chronic myeloid leukemia
Scientist may have discovered an alternative way to treat chronic myeloid leukemia, also known as CML. CML is one of the four main types of “cancer of the blood” that affects approximately 24,800 people in the United States and is characterized by the transformation of a single stem cell due to a genetic defect, which allows the stem cell to proliferate into immature and abnormal amounts of white blood cells. (1,2) Current treatments such as tyrosine kinase inhibitors (TKIs) exist that suppress the protein but do not cure the disease. Recent data has shown that many patients of CML have become resistant to the TKIs due to unknown reasons, and new treatments need to be investigated.
Jaras et al have released from their study that a possible solution to the problem is to target the proliferating CML stem cells using a cell surface biomarker known as IL-1 receptor accessory protein (IL1RAP). IL1RAP was identified using gene-expression profiling of undifferentiated CML stem cells from untreated CML patients and comparing them to normal hematopoietic stem cells (HSC) from healthy bone marrow donors. Further tests confirmed IL1RAP is found in 99.9% of CML stem cells with the genetic defect. To further demonstrate its therapeutic relevance, Jaras et al identified an antibody that can be directed towards killing the CML cells by using human natural killer cells as the effector cell.
Even though the results from this study appear promising, the process is not one hundred percent. Less than three percent of CML stem cells lacked IL1RAP and in one case a mutation in the genetic defect showed a decreased expression of IL1RAP, making it an ineffective marker for antibody targeting. But the authors state that these events are extremely rare and should not defer further research in the mechanism of antibody targeting. It is the authors' belief that "the concept of antibody-mediated killing of IL1RAP-expressing CML stem cells may also have the potential to eradicate such cells in patients, either alone or in combination with current regiments, ultimately leading to a cure for CML patients.”
Scientist may have discovered an alternative way to treat chronic myeloid leukemia, also known as CML. CML is one of the four main types of “cancer of the blood” that affects approximately 24,800 people in the United States and is characterized by the transformation of a single stem cell due to a genetic defect, which allows the stem cell to proliferate into immature and abnormal amounts of white blood cells. (1,2) Current treatments such as tyrosine kinase inhibitors (TKIs) exist that suppress the protein but do not cure the disease. Recent data has shown that many patients of CML have become resistant to the TKIs due to unknown reasons, and new treatments need to be investigated.
Jaras et al have released from their study that a possible solution to the problem is to target the proliferating CML stem cells using a cell surface biomarker known as IL-1 receptor accessory protein (IL1RAP). IL1RAP was identified using gene-expression profiling of undifferentiated CML stem cells from untreated CML patients and comparing them to normal hematopoietic stem cells (HSC) from healthy bone marrow donors. Further tests confirmed IL1RAP is found in 99.9% of CML stem cells with the genetic defect. To further demonstrate its therapeutic relevance, Jaras et al identified an antibody that can be directed towards killing the CML cells by using human natural killer cells as the effector cell.
Even though the results from this study appear promising, the process is not one hundred percent. Less than three percent of CML stem cells lacked IL1RAP and in one case a mutation in the genetic defect showed a decreased expression of IL1RAP, making it an ineffective marker for antibody targeting. But the authors state that these events are extremely rare and should not defer further research in the mechanism of antibody targeting. It is the authors' belief that "the concept of antibody-mediated killing of IL1RAP-expressing CML stem cells may also have the potential to eradicate such cells in patients, either alone or in combination with current regiments, ultimately leading to a cure for CML patients.”
Click on pdf below to view the full article
| jaras_et_al_2010.pdf |
References
1. http://www.lls.org/all_page?item_id=8501
2. Lictman, M.A., Kipps, T.J., Seligsohn, U., Kaushansk, K., and Prchal, J.T. Chapter 90. Chronic Myelogenous Leukemia and Related Disorders. Williams Hematology, 8e. http://www.accessmedicine.com.ezproxy.library.wisc.edu/content.aspx?aid=6124901
3. Jaras, M., Johnels, P., Hansen, N., Agerstam, H., Tsapogas, P., Rissler, M., Lassen, C., Olofsson, T., Bjerrum, O. W., Richter, J., & Fioretos, T. (2010). Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. PNAS, 107, 16280-16285.
2. Lictman, M.A., Kipps, T.J., Seligsohn, U., Kaushansk, K., and Prchal, J.T. Chapter 90. Chronic Myelogenous Leukemia and Related Disorders. Williams Hematology, 8e. http://www.accessmedicine.com.ezproxy.library.wisc.edu/content.aspx?aid=6124901
3. Jaras, M., Johnels, P., Hansen, N., Agerstam, H., Tsapogas, P., Rissler, M., Lassen, C., Olofsson, T., Bjerrum, O. W., Richter, J., & Fioretos, T. (2010). Isolation and killing of candidate chronic myeloid leukemia stem cells by antibody targeting of IL-1 receptor accessory protein. PNAS, 107, 16280-16285.
