Therapy for leukemia

Abstract

A pharmaceutically acceptable composition and method for leukemia therapy in a patient in need of such therapy. The composition contains, as the only active agents, the combination of (a) an inhibitor of c-Fos, (b) an inhibitor of Dusp-1, and (c) an inhibitor of BCR-ABL tyrosine kinase. The composition is administered to the patient in a dosing regimen for a period sufficient to provide therapy for leukemia.

What is claimed is: 
     
         1 . A method of therapy for leukemia in a patient, the method comprising administering to the patient in need thereof a composition containing at least one biocompatible excipient and, as the only active agents, a combination of
 (a) an inhibitor of c-Fos,   (b) an inhibitor of Dusp-1, and   (c) an inhibitor of BCR-ABL tyrosine kinase,   
       the composition administered to the patient in a dosing regimen for a period sufficient to provide therapy to the patient in need thereof. 
     
     
         2 . The method of  claim 1  where (a) is an inhibitor of a c-Fos gene, (b) is an inhibitor of a Dusp-1 gene, and (c) is an inhibitor of a BCR-ABL tyrosine kinase gene. 
     
     
         3 . The method of  claim 1  where (a) is an inhibitor of a c-Fos protein, (b) is an inhibitor of a Dusp-1 protein, and (c) is an inhibitor of a BCR-ABL tyrosine kinase protein. 
     
     
         4 . The method of  claim 1  where (a) is selected from the group consisting of curcumin, difluorinated curcumin (DFC), [3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl) methoxy]phenyl}propionic acid] (T5224), nordihydroguaiaretic acid (NDGA), dihydroguaiaretic acid (DHGA), [(E,E,Z,E)-3-methyl-7-(4-methylphenyl)-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid (SR11302), and combinations thereof; (b) is selected from the group consisting of (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), TPI-2, TPI-3, triptolide, and combinations thereof; and (c) is selected from the group consisting of Imatinib, Nilotinib, Dasatinib, Ponatinib, and combinations thereof. 
     
     
         5 . The method of  claim 4  where (a) is curcumin, (b) is BCI; and (c) is Imatinib. 
     
     
         6 . The method of  claim 4  where (a) is NDGA, (b) is BCI; and (c) is Imatinib. 
     
     
         7 . The method of  claim 4  where (a) is T5224, (b) is BCI; and (c) is Imatinib. 
     
     
         8 . The method of  claim 4  where (a) is difluorinated curcumin (DFC), (b) is BCI; and (c) is Imatinib. 
     
     
         9 . The method of  claim 1  where (a) is administered at a concentration of 2 grams per day to 8 grams per day, inclusive; (b) is administered at a concentration of 100 mg per day to 600 mg per day, inclusive; and (c) is administered at a concentration of 400 mg per day to 800 mg per day, inclusive. 
     
     
         10 . The method of  claim 1  where the composition is administered to the patient for 30 days. 
     
     
         11 . The method of  claim 1  where the composition is administered to the patient intravenously, orally, transdermally, intramuscularly, and/or intraperitoneally to result in an effective dosing regimen. 
     
     
         12 . The method of  claim 1  where the composition is administered as a cocktail. 
     
     
         13 . The method of  claim 1  where the patient has chronic myelogenous leukemia. 
     
     
         14 . The method of  claim 1  wherein the patient has acute myelogenous leukemia. 
     
     
         15 . A pharmaceutically acceptable composition comprising at least one biocompatible excipient and, as the only active agents, Imatinib, (E)-2-benzylidene-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), and curcumin, nordihydroguaiaretic acid (NDGA), or difluorinated curcumin (DFC). 
     
     
         16 . The composition of  claim 15  where the concentration of Imatinib is 400 mg per day to 800 mg per day, inclusive; the concentration of BCI is 100 mg per day to 600 mg per day, inclusive; and the concentration of curcumin, nordihydroguaiaretic acid (NDGA), or difluorinated curcumin (DFC) is 2 grams per day to 8 grams per day, inclusive. 
     
     
         17 . A method of providing therapy to a patient with leukemia comprising administering to the patient with leukemia a composition containing a combination of at least one inhibitor for each of a c-Fos gene and/or protein, a Dusp-1 gene and/or protein, and a BCR-ABL tyrosine kinase gene and/or protein, the composition administered to the patient in a dosing regimen sufficient to eliminate leukemia infiltrating cells from the patient's blood. 
     
     
         18 . The method of  claim 17  administered to a patient with chronic myelogenous leukemia. 
     
     
         19 . The method of  claim 17  administered to a patient with acute myelogenous leukemia.