Use of various nonsteroidal anti-inflammatory drugs in chronic myeloid leukemia progression
Open Access
- Author:
- Stoudt, Jocelyn Sarah
- Area of Honors:
- Immunology and Infectious Disease
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Dr. Kumble Sandeep Prabhu, Thesis Supervisor
Dr. Pamela A. Hankey-Giblin, Thesis Honors Advisor - Keywords:
- selenium
NSAID
leukemia
prostaglandin - Abstract:
- Chronic Myeloid Leukemia (CML) is responsible for 15% of all adult leukemias and current treatments do not eliminate the disease. CML is most common in older adults over age 65 and literature suggests that many older adults who take low doses of nonsteroidal anti-inflammatory drugs (NSAIDs) may be more prone to CML. Selenium is a micronutrient that the body needs for healthy function, and has been known to have chemoprotective effects on leukemia. This study examines how NSAIDs impact the role of chemoprotective properties of selenium, particularly in targeting a key population of leukemia stem cells that cause relapse of the disease. Trspfl/flCreLysM mice are unable to make selenoproteins in macrophages, and these mice are utilized to observe whether the protective effects of selenium are dependent on selenoproteins, or if free selenium can also have the same effect on CML when selenoproteins cannot be made. RAW 267.4 murine macrophages and bone marrow derived macrophages (BMDMs) isolated from C57BL/6 mice were used to answer this question. As previously described, selenium treatment increased GPX1 expression in murine RAW 264.7 macrophages. RNA and protein analysis of primary BMDMs showed varied expression of prostaglandin (PG) synthases that are downstream of cyclooxygenases. Further research is needed to determine the long-term consequences of this observation. Trsp WT and KO BMDMs produced Δ12-PGJ2 at different levels. Interestingly, Trsp KO BMDMs showed higher levels with NSAID treatment. This could affect CML patients with Trsp gene mutations. Lipid extracts generated from Trsp BMDMs will be used to treat experimental CML cells to determine the biological significance of these findings.