LEUKEMIA METHYLATION MARKERS AND USES THEREOF
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.