Methods and compositions for cell-proliferation-related disorders

Abstract

Methods of treating and evaluating subjects having neoactive mutants of IDH (e.g., IDH1 or IDH2).

1 . A method of diagnosing a subject having a cell proliferation-related disorder or suspected of having a cell proliferation-related disorder characterized by:
 (a) the presence, distribution, or level of an IDH1 mutant enzyme that has 2HG neoactivity and has other than an Arg at residue 100; or   (b) elevated levels of 2HG due to the presence of an IDH1 mutant enzyme that has 2HG neoactivity and has other than an Arg at residue 100,   wherein said method comprises analyzing the presence, distribution, or level of 2HG in a tissue, product, or bodily fluid of said subject by mass spectroscopy analysis.   
     
     
         2 . A method of evaluating a subject for the susceptibility to a cell proliferation-related disorder characterized by:
 (a) the presence, distribution, or level of an IDH1 mutant enzyme that has 2HG neoactivity and has other than an Arg at residue 100; or   (b) elevated levels of 2HG due to the presence of an IDH1 mutant enzyme that has 2HG neoactivity and has other than an Arg at residue 100,   wherein said method comprises analyzing the presence, distribution, or level of 2HG in a tissue, product, or bodily fluid of said subject by mass spectroscopy analysis.   
     
     
         3 . The method of  claim 1  or  2 , wherein said cell proliferation-related disorder is selected from the group consisting of glioma, prostate cancer, acute lymphoblastic leukemia, myelodysplasia, and myelodysplastic syndrome. 
     
     
         4 . The method of  claim 1 ,  2  or  3 , wherein said bodily fluid is blood or plasma. 
     
     
         5 . The method of  claim 1 ,  2  or  3 , wherein the mass spectroscopy is LC-MS. 
     
     
         6 . The method of  claim 1 ,  2  or  3 , wherein the mass spectroscopy is GC-MS. 
     
     
         7 . A method of diagnosing a subject having a cell proliferation-related disorder or suspected of having a cell proliferation-related disorder characterized by:
 (a) the presence, distribution, or level of an IDH2-R140Q mutant enzyme which has 2HG neoactivity; or   (b) elevated levels of 2HG due to the presence of an IDH2-R140Q mutant enzyme having 2HG neoactivity,   wherein said method comprises analyzing the presence, distribution, or level of 2HG in a tissue, product, or bodily fluid of said subject by mass spectroscopy analysis.   
     
     
         8 . A method of evaluating a subject for the susceptibility to a cell proliferation-related disorder characterized by:
 (a) the presence, distribution, or level of an IDH2-R140Q mutant enzyme that has 2HG neoactivity; or   (b) elevated levels of 2HG due to the presence of an IDH2-R140Q mutant enzyme that has 2HG neoactivity,   wherein said method comprises analyzing the presence, distribution, or level of 2HG in a tissue, product, or bodily fluid of said subject by mass spectroscopy analysis.   
     
     
         9 . The method of  claim 7  or  8  wherein said cell proliferation-related disorder is selected from the group consisting of acute lymphoblastic leukemia and acute myelogenous leukemia. 
     
     
         10 . The method of any of  claim 7 ,  8 , or  9 , wherein said bodily fluid is blood or plasma. 
     
     
         11 . The method of any of  claim 7 ,  8 , or  9 , wherein the mass spectroscopy is LC-MS. 
     
     
         12 . The method of  claim 7 ,  8 , or  9 , wherein the mass spectroscopy is GC-MS. 
     
     
         13 . A method of evaluating a subject for the susceptibility to a cell proliferation-related disorder, said method comprising analyzing the subject or a sample from the subject for the presence, distribution, or level of 2HG, wherein the subject does not have or is not diagnosed as having 2-hydroxyglutaric aciduria, and wherein the subject has an IDH mutant enzyme selected from the group consisting of, an IDH1 mutant enzyme which has 2HG neoactivity and has other than an Arg at residue 100, and IDH2-R140Q, and evaluating bodily fluid of the subject by mass spectroscopy to identify 2HG. 
     
     
         14 . A method of diagnosing a subject having a cell proliferation-related disorder or suspected of having a cell proliferation-related disorder, said method comprising analyzing the subject or a sample from the subject for the presence, distribution, or level of 2HG, wherein the subject is not having or not diagnosed as having 2-hydroxyglutaric aciduria, and wherein the subject has an IDH mutant enzyme selected from the group consisting of, an IDH1 mutant enzyme which has 2HG neoactivity and has other than an Arg at residue 100, and IDH2-R140Q, and evaluating bodily fluid of the subject by mass spectroscopy to identify 2HG. 
     
     
         15 . The method of any of  claim 13  or  14 , wherein said cell proliferation-related disorder is selected from the group consisting of colon cancer, glioma, prostate cancer, acute lymphoblastic leukemia, myelodysplasia, myelodysplastic syndrome, acute lymphoblastic leukemia and acute myelogenous leukemia. 
     
     
         16 . The method of any of  claim 13 ,  14 , or  15 , wherein the bodily fluid of the subject is blood or plasma. 
     
     
         17 . The method of any of  claim 13 ,  14 ,  15 , or  16 , wherein the mass spectroscopy is LC-MS. 
     
     
         18 . The method of  claim 13 ,  14 ,  15 , or  16 , wherein the mass spectroscopy is GC-MS.