Compositions for treatment of acute lymphoblastic leukemia and methods of use thereof

Abstract

Provided herein are compositions for treatment of Acute Lymphoblastic Leukemia (ALL) and methods of their use, including inhibiting ALL relapse. Further provided herein are systems of treatment that are directed by a health care provider, and which combine prognostic methods for determining ALL relapse and the described treatments.

1 - 21 . (canceled) 
     
     
         22 . A method for treatment of acute lymphoblastic leukemia (ALL) in a subject, comprising:
 administering to the subject a therapeutically effective amount of an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), thereby treating the patient.   
     
     
         23 . The method of  claim 22 , wherein the inhibitor of NAMPT is selected from the group consisting of a small molecule inhibitor, antibody, antisense nucleic acid, and RNA interference agent. 
     
     
         24 . The method of  claim 22 , wherein the inhibitor is FK866 or a functional variant thereof. 
     
     
         25 . The method of  claim 22 , wherein the inhibitor is miR-541 or a ribonucleic acid sequence at least 90% identical to a miR-451 ribonucleic acid sequence set forth as SEQ ID NO: 2. 
     
     
         26 . The method of  claim 22 , wherein the treatment of ALL comprises reducing risk of relapse in a subject. 
     
     
         27 . The method of  claim 26 , wherein the subject has been diagnosed as having an intermediate risk or high risk of ALL relapse. 
     
     
         28 . A method for treatment of acute lymphoblastic leukemia (ALL) in a subject, comprising:
 administering to the subject a therapeutically effective amount of an inhibitor of miR-1290, thereby treating the patient.   
     
     
         29 . The method of  claim 28 , wherein the inhibitor of miR-1290 comprises a nucleic acid that is at least 90% identical to the reverse complement of the miR-1290 sequence as set forth in SEQ ID NO: 3. 
     
     
         30 . The method of  claim 28 , wherein the inhibitor of mir-1290 comprises a nucleic acid expressing a nucleic acid that is at least 90% identical to the reverse complement of the miR-1290 sequence as set forth in SEQ ID NO: 3. 
     
     
         31 . The method of  claim 30 , wherein the inhibitor is selected from the group consisting of a DNA inhibitor or an RNA interference (RNAi) agent. 
     
     
         32 . The method of  claim 30 , further comprising administering to the subject a therapeutically effective amount of an inhibitor of mir-1290 comprising a nucleic acid expressing a nucleic acid that is at least 90% identical to the reverse complement of the miR-1290 sequence as set forth in SEQ ID NO: 3. 
     
     
         33 . A method for treatment of acute lymphoblastic leukemia (ALL) in a subject, comprising:
 administering to the subject a therapeutically effective amount of a ribonucleic acid sequence at least 90% identical to a miR-451 ribonucleic acid sequence set forth as SEQ ID NO: 2, or a nucleic acid expressing a ribonucleic acid sequence at least 90% identical to a miR-451 ribonucleic acid sequence set forth as SEQ ID NO: 2, thereby treating the patient.   
     
     
         34 . The method of  claim 32 , wherein the nucleic acid expressing miR-451 is operably linked to a recombinant expression plasmid. 
     
     
         35 . A method for treatment of acute lymphoblastic leukemia (ALL) in a subject, comprising:
 administering to the subject a therapeutically effective amount of an inhibitor of janus kinase 2 (JAK2), thereby treating the patient.   
     
     
         36 . The method of  claim 35 , wherein the inhibitor of JAK2 is selected from the group consisting of a small molecule inhibitor, antibody, antisense nucleic acid, and RNA interference agent. 
     
     
         37 . A method of acute lymphoblastic leukemia (ALL) relapse treatment or prevention comprising:
 determining the expression level of miR-1290 and at least one of miR-151-5p and miR-451 in a subject in risk of ALL relapse; 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 a therapeutically effective amount of a composition tailored to the miRNA molecule determined to be significantly decreased (deficient) or significantly increased (overexpressed).   
     
     
         38 . The method of  claim 37 , comprising administering an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT).