{"title":"Three-dimensional chromatin landscapes in MLLr AML.","authors":"Pinpin Sui, Zhihong Wang, Peng Zhang, Feng Pan","doi":"10.1186/s40164-024-00523-5","DOIUrl":null,"url":null,"abstract":"<p><p>Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"56"},"PeriodicalIF":9.4000,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110396/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental Hematology & Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s40164-024-00523-5","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Rearrangements of the mixed lineage leukemia (MLLr) gene are frequently associated with aggressive acute myeloid leukemia (AML). However, the treatment options are limited due to the genomic complexity and dynamics of 3D structure, which regulate oncogene transcription and leukemia development. Here, we carried out an integrative analysis of 3D genome structure, chromatin accessibility, and gene expression in gene-edited MLL-AF9 AML samples. Our data revealed profound MLLr-specific alterations of chromatin accessibility, A/B compartments, topologically associating domains (TAD), and chromatin loops in AML. The local 3D configuration of the AML genome was rewired specifically at loci associated with AML-specific gene expression. Together, we demonstrate that MLL-AF9 fusion disrupts the 3D chromatin landscape, potentially contributing to the dramatic transcriptome remodeling in MLLr AML.
混合系白血病（MLLr）基因重排经常与侵袭性急性髓性白血病（AML）有关。然而，由于基因组的复杂性和三维结构的动态性调控着癌基因的转录和白血病的发展，治疗方案十分有限。在此，我们对基因编辑的 MLL-AF9 AML 样本的三维基因组结构、染色质可及性和基因表达进行了综合分析。我们的数据揭示了急性髓细胞性白血病中染色质可及性、A/B区、拓扑关联域（TAD）和染色质环的深刻的MLL特异性改变。在与 AML 特异性基因表达相关的位点，AML 基因组的局部三维结构被重新连接。总之，我们证明了 MLL-AF9 融合会破坏染色质的三维结构，从而可能导致 MLLr AML 转录组的显著重塑。
期刊介绍：
Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings.
Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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