Methods and compositions for cell-proliferation-related disorders
Methods of treating and evaluating subjects having neoactive mutants are described herein.
1. A method of treating a subject having acute myelogenous leukemia (AML) characterized by the presence of a mutant isocitrate dehydrogenase 1 enzyme (IDH1) or a mutant isocitrate dehydrogenase 2 enzyme (IDH2), wherein the mutant IDH1 or mutant IDH2 has the ability to convert alpha-ketoglutarate to 2-hydroxyglutarate (2HG), the method comprising administering to the subject a therapeutically effective amount of a small molecule inhibitor of said mutant IDH1 or mutant IDH2.
2. The method of claim 1 , wherein the inhibitor binds to IDH1R132X or IDH2R172X and inhibits the ability to convert alpha-ketoglutarate to 2-HG.
3. The method of claim 1 , wherein the cancer is characterized by an IDH1 mutation.
4. The method of claim 3 , wherein the IDH1 mutation is an IDH1R132X mutation.
5. The method of claim 3 , wherein the IDH1 mutation is selected from R132H, R132C, R132S, R132G, R132L, and R132V.
6. The method of claim 1 , wherein the cancer is characterized by an IDH2 mutation.
7. The method of claim 6 , wherein the IDH2 mutation is an IDH1R172X mutation.
8. The method of claim 6 , wherein the IDH2 mutation is selected from R172K, R172M, R172S, R172G, and R172W.
9. The method of claim 1 , wherein the mutant IDH1 or mutant IDH2 is detected in a sample obtained from the subject.
10. The method of claim 9 , wherein the sample comprises tissue or bodily fluid.
11. The method of claim 1 , wherein the mutant IDH1 or mutant IDH2 is detected by sequencing a nucleic acid from an affected cell that encodes the relevant amino acid(s) from the mutant IDH1 or mutant IDH2.
12. The method of claim 11 , wherein the sequencing is performed by polymerase chain reaction (PCR).