Methods and Compositions for Inducing Deregulation of EPHA7 and ERK Phosphorylation in Human Acute Leukemias

Abstract

Methods for assessing a pathological condition in a subject include measuring one or more markers where a difference is indicative of acute lymphoblastic leukemia (ALL) or a predisposition to ALL, uses and compositions are disclosed.

What is claimed is: 
     
         1 . A composition comprising at least one agent that interferes with an acute lymphoblastic leukemia (ALL) response signaling pathway in at least one leukemic cell producing an ALL1/AF9 chimeric fusion protein, wherein the agent comprises:
 an isolated or synthetic ALL1/AF9-specific siRNA which suppresses expression of an ALL1/AF9 chimeric fusion protein; and   an isolated or synthetic EphA7-specific siRNA which suppresses expression of EphA7.   
     
     
         2 . The composition according to  claim 1 , wherein the isolated or synthetic ALL1/AF9-specific siRNA is an SEMj siRNA. 
     
     
         3 . The composition according to  claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA. 
     
     
         4 . The composition according to  claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#2 siRNA. 
     
     
         5 . The composition according to  claim 1 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA and an siEphA7#2 siRNA. 
     
     
         6 . The composition according to  claim 1 , further comprising: 5-iodotubercidin. 
     
     
         7 . The composition according to  claim 1 , wherein the agent is a-synthetic ALL1/AF9-specific siRNA, and a synthetic EphA7-specific siRNA. 
     
     
         8 . The composition according to  claim 1 , wherein the isolated or synthetic ALL1/AF9-specific siRNA is an SEMj siRNA, and the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof. 
     
     
         9 . The composition according to  claim 7 , wherein the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof. 
     
     
         10 . The composition according to  claim 1 , wherein at least two isolated or synthetic EphA7-specific siRNA targets EphA7 mRNA at two distinct regions. 
     
     
         11 . The composition according to  claim 10 , wherein the isolated or synthetic ALL1/AF9-specific siRNA is an SEMj siRNA, and the isolated or synthetic EphA7-specific siRNA is an siEphA7#1 siRNA, an siEphA7#2 siRNA, or a combination thereof. 
     
     
         12 . The composition according to  claim 1 , wherein the leukemic cell is at least one leukemic cell selected from the group consisting of a K562 leukemic cell transfected with an ALL1/AF9 chimeric fusion protein construct; a pro-B leukemic SEMK2 cell having a t(4; 11) chromosome translocation; and a pro-B leukemic RS4 cell having a t(4; 11) chromosome translocation.