{"id":1935,"date":"2025-01-14T11:08:27","date_gmt":"2025-01-14T02:08:27","guid":{"rendered":"https:\/\/www.nobomedicine.com\/?post_type=publication&#038;p=1935"},"modified":"2025-01-14T11:11:11","modified_gmt":"2025-01-14T02:11:11","slug":"increased-local-dna-methylation-disorder-in-amls-with-dnmt3a-destabilizing-variants-and-its-clinical-implication","status":"publish","type":"publication","link":"http:\/\/www.nobomedicine.com\/?publication=increased-local-dna-methylation-disorder-in-amls-with-dnmt3a-destabilizing-variants-and-its-clinical-implication","title":{"rendered":"Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\" id=\"Abs1\">Abstract<\/h2>\n\n\n\n<p>The mechanistic link between the complex mutational landscape of de novo methyltransferase&nbsp;<em>DNMT3A<\/em>&nbsp;and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (<em>DNMT3A<\/em><sup>INS<\/sup>) in AML, we here investigate the common characteristics of&nbsp;<em>DNMT3A<\/em><sup>INS<\/sup>&nbsp;AML methylomes through computational analyses. We present that methylomes of&nbsp;<em>DNMT3A<\/em><sup>INS<\/sup>&nbsp;AMLs are considerably different from those of&nbsp;<em>DNMT3A<\/em><sup>R882<\/sup>&nbsp;AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains. This epigenetic heterogeneity was associated with the transcriptional variability of developmental and membrane-associated factors shaping stem cell niche, and also was a predictor of the response of AML cells to hypomethylating agents, implying that the survival of AML cells depends on stochastic DNA methylations at bivalent domains. Altogether, our work provides a novel mechanistic model suggesting the genomic origin of the aberrant epigenomic heterogeneity in disease conditions.<\/p>\n","protected":false},"featured_media":0,"parent":0,"template":"","class_list":["post-1935","publication","type-publication","status-publish","hentry"],"_links":{"self":[{"href":"http:\/\/www.nobomedicine.com\/index.php?rest_route=\/wp\/v2\/publication\/1935","targetHints":{"allow":["GET"]}}],"collection":[{"href":"http:\/\/www.nobomedicine.com\/index.php?rest_route=\/wp\/v2\/publication"}],"about":[{"href":"http:\/\/www.nobomedicine.com\/index.php?rest_route=\/wp\/v2\/types\/publication"}],"wp:attachment":[{"href":"http:\/\/www.nobomedicine.com\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1935"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}