Biomarkers of chronic lymphocytic leukemia and use thereof

Abstract

The present invention provides novel biomarkers of chronic lymphocytic leukemia (CLL). Specifically, the present invention provides methods and kits for diagnosing, assessing the level of severity, and treating of CLL.

1 . A kit for diagnosing chronic lymphocytic leukemia (CLL) in a patient, predicting or assessing the level of CLL severity, predicting CLL progression, and/or determining the treatment regimen in a patient diagnosed with CLL, comprising:
 (i) at least one agent or means capable of detecting the expression level of at least one protein or mRNA biomarker selected from the group consisting of ISG20, SLC25A1, SNX18, DHRS4, TBL2, RPE, ENPP4, NOP56, PSMC5, CTSS, APRT, PPP2R1A, CABIN1, HP1BP3, GCD, RPL13A, UBE3A, and MRPS22, in a biological sample obtained from a subject diagnosed to have or suspected of having CLL; and   (ii) means for comparing the expression level of the at least one biomarker in the sample to the expression level in a reference value or a control sample.   
     
     
         2 . The kit of  claim 1 , wherein the kit comprises means for detecting a plurality of the protein or mRNA biomarkers. 
     
     
         3 . The kit of  claim 1 , wherein the kit further comprising instruction material directing the correlation between the compared expression levels of said at least one biomarker and the level of severity of CLL. 
     
     
         4 . The kit of  claim 3 , wherein an increase in the expression level of at least one biomarker selected from the group consisting of: ISG20, SLC25A1, SNX18, DHRS4, TBL2, RPE, NOP56, PSMC5, CTSS, APRT, PPP2R1A, CABIN1, HP1BP3, GCD, RPL13A, UBE3A, MRPS22, and any combination thereof and/or a decrease in the level of ENPP4 in the sample obtained from the subject compared to the reference value or control sample characterizes said patient as having a severe form of chronic lymphocytic leukemia. 
     
     
         5 . The kit of  claim 1 , further comprising at least one agent or means capable of detecting the expression level of at least one ACOX3 protein or mRNA biomarker. 
     
     
         6 . The kit of  claim 1 , wherein the biomarker is a protein marker and wherein said kit comprises at least one reagent for performing an ELISA, an RIA, a slot blot, an immunohistochemical assay, FACS, in vivo imaging, a radio-imaging assay, a microarray, or a Western blot. 
     
     
         7 . The kit of  claim 6 , wherein a plate of the ELISA is pre-coated with specific antibodies for the at least one biomarker. 
     
     
         8 . The kit of  claim 2 , wherein the means for detecting is an antibody array comprising at least one specific antibody for the at least one biomarker. 
     
     
         9 . The kit of  claim 8 , wherein the antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a chimeric antibody, a human antibody, an affinity maturated antibody and antibody fragment. 
     
     
         10 . The kit of  claim 8 , wherein the antibody array is a microarray comprising antibodies specific for the plurality of the at least one biomarker. 
     
     
         11 . The kit of  claim 1 , wherein the biomarker is an mRNA biomarker and the kit further comprises means for Nucleic acid testing (NAT) Assays. 
     
     
         12 . The kit of  claim 1 , wherein diagnosing includes early diagnosis of CLL in a patient. 
     
     
         13 . The kit of  claim 1 , wherein the kit is useful for providing guidance for treatment to a patient characterized as having CLL.