MLL translocations specify a distinct gene expression profile, distinguishing a unique leukemia

Abstract

The present invention relates to the diagnosis of mixed lineage leukemia (MLL), acute lymphoblastic leukemia (ALL), and acute myelogenous leukemia (AML) according to the gene expression profile of a sample from an individual, as well as to methods of therapy and screening that utilize the genes identified herein as targets.

1 . A method of distinguishing between mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia, comprising determining a gene expression profile of a gene expression product from at least one informative gene from one or more cells from an individual suspected to have mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia, wherein the cells are selected from the group consisting of mononuclear blood cells and bone marrow cells, and wherein the gene expression profile is correlated with mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia.  
   
   
       2 . The method of  claim 1 , wherein the gene expression product is RNA.  
   
   
       3 . The method of  claim 2 , wherein the gene expression profile is determined utilizing specific hybridization probes.  
   
   
       4 . The method of  claim 2 , wherein the gene expression profile is determined utilizing oligonucleotide microarrays.  
   
   
       5 . The method of  claim 1 , wherein the gene expression product is a peptide.  
   
   
       6 . The method of  claim 5 , wherein the gene expression profile is determined utilizing antibodies.  
   
   
       7 . The method of  claim 1 , wherein said at least one informative gene is selected from the group consisting of the genes in  FIGS. 1A, 1B ,  2 A- 2 F,  3 A- 3 D, and  5 , and Tables 1 and 2.  
   
   
       8 . The method of  claim 1 , comprising determining a gene expression profile of the gene expression product from at least 2 informative genes.  
   
   
       9 . The method of  claim 1 , comprising determining a gene expression profile of the gene expression product from at least 4 informative genes.  
   
   
       10 . The method of  claim 1 , comprising determining a gene expression profile of the gene expression product from at least 10 informative genes.  
   
   
       11 . A method of distinguishing between mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia, comprising: 
 a) determining a gene expression profile of mRNA from at least one informative gene, wherein the mRNA is isolated from one or more cells of an individual suspected to have mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia and selected from the group consisting of mononuclear blood cells and bone marrow cells; and    b) comparing the gene expression profile of a) to a gene expression profile of a control sample selected from the group consisting of a mixed lineage leukemia sample, an acute lymphoblastic leukemia sample and an acute myelogenous leukemia sample, wherein the gene expression profile of a) is indicative of mixed lineage leukemia, acute lymphoblastic leukemia or acute myelogenous leukemia.    
   
   
       12 . The method of  claim 11 , comprising determining a gene expression profile of the gene expression product from at least 2 informative genes.  
   
   
       13 . The method of  claim 11 , comprising determining a gene expression profile of the gene expression product from at least 4 informative genes.  
   
   
       14 . The method of  claim 11 , comprising determining a gene expression profile of the gene expression product from at least 10 informative genes.  
   
   
       15 . A method of diagnosing mixed lineage leukemia, comprising determining a gene expression profile of a gene expression product from at least one informative gene from one or more cells selected from the group consisting of mononuclear cells and bone marrow cells of an individual, wherein the gene expression profile is correlated with mixed lineage leukemia.  
   
   
       16 . The method of  claim 15 , wherein the informative gene is selected from the group consisting of FLT3, MEIS1 and HoxA9.  
   
   
       17 . The method of  claim 15 , comprising determining a gene expression profile of the gene expression product from at least 2 informative genes.  
   
   
       18 . The method of  claim 15 , comprising determining a gene expression profile of the gene expression product from at least 4 informative genes.  
   
   
       19 . The method of  claim 15 , comprising determining a gene expression profile of the gene expression product from at least 10 informative genes.