{"title":"Chromatin and aberrant enhancer activity in KMT2A rearranged acute lymphoblastic leukemia","authors":"Thomas A Milne","doi":"10.1016/j.gde.2024.102191","DOIUrl":null,"url":null,"abstract":"<div><p>To make a multicellular organism, genes need to be transcribed at the right developmental stages and in the right tissues. DNA sequences termed ‘enhancers’ are crucial to achieve this. Despite concerted efforts, the exact mechanisms of enhancer activity remain elusive. <em>Mixed lineage leukemia</em> (<em>MLL</em> or <em>KMT2A</em>) rearrangements (MLLr), commonly observed in cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, produce novel in-frame fusion proteins. Recent work has shown that the MLL-AF4 fusion protein drives aberrant enhancer activity at key oncogenes in ALL, dependent on the continued presence of MLL-AF4 complex components. As well as providing some general insights into enhancer function, these observations may also provide an explanation for transcriptional heterogeneity observed in MLLr patients.</p></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"86 ","pages":"Article 102191"},"PeriodicalIF":3.7000,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959437X24000406/pdfft?md5=a5161d94b242766d396add9a0de2fd94&pid=1-s2.0-S0959437X24000406-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Genetics & Development","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959437X24000406","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
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Abstract
To make a multicellular organism, genes need to be transcribed at the right developmental stages and in the right tissues. DNA sequences termed ‘enhancers’ are crucial to achieve this. Despite concerted efforts, the exact mechanisms of enhancer activity remain elusive. Mixed lineage leukemia (MLL or KMT2A) rearrangements (MLLr), commonly observed in cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia, produce novel in-frame fusion proteins. Recent work has shown that the MLL-AF4 fusion protein drives aberrant enhancer activity at key oncogenes in ALL, dependent on the continued presence of MLL-AF4 complex components. As well as providing some general insights into enhancer function, these observations may also provide an explanation for transcriptional heterogeneity observed in MLLr patients.
期刊介绍：
Current Opinion in Genetics and Development aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed.
In Current Opinion in Genetics and Development we help the reader by providing in a systematic manner:
1. The views of experts on current advances in their field in a clear and readable form.
2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.[...]
The subject of Genetics and Development is divided into six themed sections, each of which is reviewed once a year:
• Cancer Genomics
• Genome Architecture and Expression
• Molecular and genetic basis of disease
• Developmental mechanisms, patterning and evolution
• Cell reprogramming, regeneration and repair
• Genetics of Human Origin / Evolutionary genetics (alternate years)
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