Leukemia methylation markers and uses thereof

Abstract

Disclosed herein are methods and kits for identifying a subject as having leukemia. Also provided herein are methods and kits for determining a leukemia subtype in subject. Further provided herein are methods and kits for determining the prognosis of a subject having leukemia and for determining the progression of leukemia in a subject.

1 - 20 . (canceled) 
     
     
         21 : A method of detecting a methylation pattern of a set of biomarkers in a subject suspected of having acute myeloid leukemia, the method comprising:
 (a) processing an extracted genomic DNA with a deaminating agent to generate a genomic DNA sample comprising deaminated nucleotides,
 wherein the extracted genomic DNA is obtained from a biological sample from the subject suspected of having acute myeloid leukemia; and 
   (b) detecting the methylation pattern of the set of biomarkers from the processed extracted genomic DNA,
 wherein the set of biomarkers comprises: cg01628067, cg03001333, cg04984818, cg05145233, cg05304729, cg05956452, cg06261066, cg09157302, cg14608384, cg15289427, cg15608301, cg15707093, cg16266227, cg18869709, cg19470372, cg19864130, cg20686234, cg21913319, cg24720672, cg24747122, cg24983367, cg26584619, and cg27178401. 
   
     
     
         22 : The method of  claim 21 , further comprising obtaining a methylation score from the methylation pattern of the set of biomarkers. 
     
     
         23 : The method of  claim 22 , wherein the methylation score is calculated based on Cox proportional hazards (PH) regression analysis. 
     
     
         24 : The method of  claim 21 , wherein the acute myeloid leukemia is metastatic acute myeloid leukemia. 
     
     
         25 : The method of  claim 21 , further comprising extracting genomic DNA from the biological sample to obtain an extracted genomic DNA. 
     
     
         26 : The method of  claim 21 , further comprising contacting the processed extracted genomic DNA with a set of probes, wherein the set of probes comprises a probe that hybridizes to each of the set of biomarkers, and performing a DNA sequencing analysis to detect the methylation pattern of the set of biomarkers. 
     
     
         27 : The method of  claim 21 , wherein the detecting of the methylation pattern comprises a next-generation sequencing technique. 
     
     
         28 : The method of  claim 27 , wherein the next-generation sequencing technique is a digital PCR sequencing method. 
     
     
         29 : The method of  claim 21 , wherein the detecting of the methylation pattern comprises performing a DNA sequencing reaction to detect the methylation pattern of the set of biomarkers. 
     
     
         30 : A method of treating a subject having an acute myeloid leukemia, the method comprising administering a first treatment of an effective amount of a therapeutic agent to the subject,
 wherein the subject is selected for the first treatment based on having a methylation score based on a methylation profile of a set of biomarkers comprising: cg01628067, cg03001333, cg04984818, cg05145233, cg05304729, cg05956452, cg6261066, cg09157302, cg14608384, cg15289427, cg15608301, cg15707093, cg16266227, cg18869709, cg19470372, cg19864130, cg20686234, cg21913319, cg24720672, cg24747122, cg24983367, cg26584619, and cg27178401.   
     
     
         31 : The method of  claim 30 , further comprising obtaining the methylation score from the methylation pattern of the set of biomarkers. 
     
     
         32 : The method of  claim 30 , wherein the methylation score is calculated based on Cox proportional hazards (PH) regression analysis. 
     
     
         33 : The method of  claim 30 , further comprising obtaining the methylation pattern of the set of biomarkers. 
     
     
         34 : The method of  claim 33 , wherein obtaining the methylation pattern of the set of biomarkers comprises:
 (a) processing an extracted genomic DNA with a deaminating agent to generate a genomic DNA sample comprising deaminated nucleotides,
 wherein the extracted genomic DNA is obtained from a biological sample from the subject; and 
   (b) detecting the methylation pattern of the set of biomarkers from the processed extracted genomic DNA.   
     
     
         35 : The method of  claim 34 , further comprising contacting the processed extracted genomic DNA with a set of probes, wherein the set of probes comprises a probe that hybridizes to each of the set of biomarkers, and performing a DNA sequencing analysis to detect the methylation pattern of the set of biomarkers. 
     
     
         36 : The method of  claim 30 , wherein the acute myeloid leukemia is metastatic acute myeloid leukemia. 
     
     
         37 : A kit comprising a set of nucleic acid probes, wherein the set of nucleic acid probes comprises a probe that hybridizes to each of a set of biomarkers comprising: cg01628067, cg03001333, cg04984818, cg05145233, cg05304729, cg05956452, cg6261066, cg9157302, cg14608384, cg15289427, cg15608301, cg15707093, cg16266227, cg18869709, cg19470372, cg19864130, cg20686234, cg21913319, cg24720672, cg24747122, cg24983367, cg26584619, and cg27178401. 
     
     
         38 : The kit of  claim 37 , wherein the set of nucleic acid probes comprises a next-generation sequencing probe. 
     
     
         39 : The kit of  claim 38 , wherein the set of nucleic acid probes comprises a droplet digital PCR probe.