Prognostic methods and systems of treatment for acute lymphoblastic leukemia

Abstract

Described herein are methods for determining the prognosis of a patient diagnosed with Acute Lymphoblastic Leukemia (ALL), and particularly determining the risk of disease relapse following standard treatment. Also described are systems of treatment that are directed by a health care provider, and which include the described prognostic methods and the treatments recommended for patients determined to have a specific relapse risk.

1 . A method of prognosis of acute lymphoblastic leukemia (ALL) in a subject, comprising:
 determining the expression level of miR-1290 in a sample from the subject; and   comparing the miR-1290 expression level in the subject with control expression of miR-1290,   wherein a significant increase in miR-1290 expression in the subject in comparison to the control expression indicates that the subject has an increased risk of ALL relapse; and   wherein a significant decrease in miR-1290 expression in the subject in comparison to the control expression indicates that the subject has a reduced risk of ALL relapse.   
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the control expression of miR-1290 is a cutoff value. 
     
     
         4 . (canceled) 
     
     
         5 . The method of  claim 1 , wherein the risk of ALL relapse in the subject is further correlated with ALL-associated clinical criteria selected from the group consisting of: B-ALL and T-ALL diagnosis, minimal residual disease (MRD) high and low risk definitions, response to prednisone on day 8 of treatment; BFM high and low risk definitions, white blood count (WBC) being over or below 20,000 cells/ml, patient age being over one and under six years old or otherwise, COG high and standard risk definitions for induction therapy, COG low/average/high/very high risk definitions for post-induction therapy, and gender. 
     
     
         6 . The method of  claim 1 , wherein the subject has been diagnosed with B-ALL. 
     
     
         7 . The method of  claim 1 , wherein the sample is isolated from bone marrow or blood of the subject. 
     
     
         8 . The method of  claim 1 , wherein the determination that a subject has an increased risk of ALL relapse predicts that the subject could benefit from a treatment comprising at least of a NAMPT or JAK2 inhibitor. 
     
     
         9 . The method of  claim 1 , wherein the method is repeated at least once after the initiation of ALL therapy, and wherein a change in prognosis is thereby monitored. 
     
     
         10 . A system of ALL treatment comprising:
 determining the expression level of miR-1290 in a sample from the subject;   comparing the miR-1290 expression level in the subject with control expression of miR-1290,
 wherein a significant increase in miR-1290 expression in the subject in comparison to the control expression indicates that the subject has an increased risk of ALL relapse, and requires treatment appropriate for a subject with an increased risk of ALL relapse; and 
   administering to the patient an ALL treatment designated as appropriate for a patient with an increased risk of ALL relapse.   
     
     
         11 . A system of ALL treatment comprising:
 determining the expression level of miR-1290 and at least one of miR-151-5p and miR-451; and   comparing the determined expression of miR-1290, and miR-151-5p and/or miR-451 with control expression of miR-1290, and miR-151-5p and/or miR-451,
 wherein a significant increase in miR-1290 expression in the subject in comparison to the control miR-1290 expression, combined with a significant decrease in expression of the at least one of miR-151-5p and miR-451 in comparison to the control expression of miR-151-5p and/or miR-451, indicates that the subject has an increased risk of ALL relapse, and requires treatment appropriate for a subject with an increased risk of ALL relapse; and 
   administering to the patient an ALL treatment designated as appropriate for a patient with an increased risk of ALL relapse.   
     
     
         12 . The system of  claim 10 , wherein the control expression of miR-1290 is a cutoff value. 
     
     
         13 . The system of  claim 11 , wherein the control expression of miR-1290, miR-151-5p, and miR-451 are separate cutoff values. 
     
     
         14 . The system of any one of  claim 10 , wherein the risk of ALL relapse in the subject is further correlated with ALL-associated clinical criteria selected from the group consisting of: B-ALL and T-ALL diagnosis, minimal residual disease (MRD) high and low risk definitions, response to prednisone on day 8 of treatment; BFM high and low risk definitions, white blood count (WBC) being over or below 20,000 cells/ml, patient age being over one and under six years old or otherwise, CCG high and low risk definitions, and gender. 
     
     
         15 . The system of any one of  claim 10 , wherein the subject has been diagnosed with B-ALL. 
     
     
         16 . The system of  claim 10 , wherein the sample is isolated from bone marrow or blood of the subject. 
     
     
         17 . The system of  claim 10 , wherein the subject has an standard risk of relapse or a high risk of relapse. 
     
     
         18 . The system of  claim 10 , wherein the treatment is a protocol for patients determined to have a high risk of ALL relapse. 
     
     
         19 . The system of  claim 18 , wherein the treatment includes a composition comprising an anthracycline.