Method of treating and reducing the risk of acute myelogenous leukemia
The present invention relates to methods and compositions for treating and reducing the risk of Acute Myelogenous Leukemia (AML). In particular, the invention provides methods for identifying novel treatments for AML based on reproducible and detectable changes in AML1-ETO acetylation. The present invention further provides methods of using these treatments.
1. A method of identifying agents for treating or reducing risk for acute myelogenous leukemia comprising:
providing a system comprising at least AML1-ETO and p300, in which AML1-ETO acetylation level is determinable;
contacting the system with a test agent;
determining AML1-ETO acetylation level when the test agent is present;
comparing the determined AML1-ETO acetylation level with a reference AML1-ETO acetylation level so that any difference between the reference level and the determined level is detected; and
characterizing the test agent's usefulness in treating or reducing risk for acute myelogenous leukemia based on the detected difference.
2. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions lacking the test agent.
3. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in the system under otherwise identical conditions lacking the test agent.
4. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions that include presence of a positive control agent.
5. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in the system under comparable conditions that include presence of a negative control agent.
6. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions lacking the test agent.
7. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in a comparable system under otherwise identical conditions lacking the test agent.
8. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions that include presence of a positive control agent.
9. The method of claim 1 , wherein the reference AML1-ETO acetylation level is that observed in a comparable system under comparable conditions that include presence of a negative control agent.
10. The method of claim 1 , wherein the reference AML1-ETO acetylation level is a historical level.
11. The method of claim 1 , wherein the system is an in vitro system.
12. The method of claim 11 wherein the in vitro system comprises cultured cells.
13. The method of claim 12 wherein the cultured cells comprise acute myelogenous leukemia cells.
14. The method of claim 12 wherein the cultured cells are transfected with a vector containing no insert or the vector containing AML1-ETO (SEQ ID NO.1).
15. The method of claim 1 , wherein the system is an in vivo system.
16. The method of claim 15 wherein the in vivo system comprises mice expressing AML1-ETO (SEQ ID NO. 1).
17. The method of claim 1 , wherein the acetylation level of AML1-ETO comprises acetylation on amino acid K43.