Event Title
Testing the efficacy of new nucleoside analogues against Acute Myeloid Leukemia
Year of Study
Third year
Abstract
Acute Myeloid Leukemia (AML) is a rapidly-proliferating and aggressive cancer of the bone marrow, currently treated using chemotherapy drugs, such as Cytarabine. As a nucleoside analogue, Cytarabine effectively decreases cell viability and induces apoptosis by damaging nuclear DNA during the S phase of the cell cycle. Drugs continue to be developed to further improve AML patient prognosis, including those created by Medivir™, a Swedish drug company. The goal of this project was to test the efficacy of two preclinical nucleoside analogue drugs designed by Medivir™, MV087320-1 and MV087924-1. This was done by analyzing cell viability and DNA damage mechanisms in vitro within AML cell lines and patient samples. Considering that MV087320-1 and MV087924-1 are designed to mimic the action of Cytarabine, we hypothesized that drug treatments with AML cells will reduce cell viability and increase upregulation of DNA-damage marker proteins, such as Phospho H2A.X. The drugs were tested across a panel of cell lines and patient samples using Cytarabine as a positive control. The results measuring cell viability showed that MV087320-1 was more effective than Cytarabine, whereas MV087924-1 proved the least effective in vitro, possibly due to its role as the prodrug of MV087320-1. Phospho H2A.X protein levels were upregulated in cells treated with MV087320-1, indicating that the drug successfully induced DNA damage. Moving forward, the drugs’ in vitro effects will be compared with their in vivo effects and future experiments will continue to study the drugs’ mechanism(s), to ultimately determine if the drugs are effective treatments against AML.
Presentation Type
Poster Presentation
Testing the efficacy of new nucleoside analogues against Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML) is a rapidly-proliferating and aggressive cancer of the bone marrow, currently treated using chemotherapy drugs, such as Cytarabine. As a nucleoside analogue, Cytarabine effectively decreases cell viability and induces apoptosis by damaging nuclear DNA during the S phase of the cell cycle. Drugs continue to be developed to further improve AML patient prognosis, including those created by Medivir™, a Swedish drug company. The goal of this project was to test the efficacy of two preclinical nucleoside analogue drugs designed by Medivir™, MV087320-1 and MV087924-1. This was done by analyzing cell viability and DNA damage mechanisms in vitro within AML cell lines and patient samples. Considering that MV087320-1 and MV087924-1 are designed to mimic the action of Cytarabine, we hypothesized that drug treatments with AML cells will reduce cell viability and increase upregulation of DNA-damage marker proteins, such as Phospho H2A.X. The drugs were tested across a panel of cell lines and patient samples using Cytarabine as a positive control. The results measuring cell viability showed that MV087320-1 was more effective than Cytarabine, whereas MV087924-1 proved the least effective in vitro, possibly due to its role as the prodrug of MV087320-1. Phospho H2A.X protein levels were upregulated in cells treated with MV087320-1, indicating that the drug successfully induced DNA damage. Moving forward, the drugs’ in vitro effects will be compared with their in vivo effects and future experiments will continue to study the drugs’ mechanism(s), to ultimately determine if the drugs are effective treatments against AML.
Questions
Not applicable.