Understanding of molecular pathogenesis of T-cell leukemia by super-enhancer profiling

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  • SANDA Takaomi
    Cancer Science Institute of Singapore, National University of Singapore Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore

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Other Title
  • スーパーエンハンサープロファイリングによるT細胞性白血病の分子病態の理解
  • スーパーエンハンサープロファイリング ニ ヨル Tサイボウセイ ハッケツビョウ ノ ブンシ ビョウタイ ノ リカイ

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<p>Super-enhancers comprise of clusters of enhancers that are typically defined by the ChIP-seq analysis for active histone marks. Although the biological significance of super-enhancers is still controversial, this concept is gaining prominence as useful characteristics of genes that play crucial roles in normal development and pathogenesis of cancer. In various cancer cells, super-enhancers are often associated with genes involved in carcinogenesis. For example, in T-cell acute lymphoblastic leukemia, the oncogenic transcription factor TAL1 and its regulatory partners (GATA3, RUNX1 and MYB) are regulated by super-enhancers; these genes are sensitive to transcriptional inhibition, for example, via the pharmacological approach using a small-molecule CDK7 inhibitor. This preferential inhibition of cancer genes can also be observed for other types of cancer. Based on these findings, we recently performed super-enhancer profiling combined with gene expression analysis in adult T-cell leukemia/lymphoma, which is a genetically complicated hematological malignancy, to identify critical genes responsible for the pathogenesis. This review article aims to discuss the concept of super-enhancers, their significance in biomedical research, and their potential utility in elucidating the molecular pathogenesis of cancer.</p>

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  • Rinsho Ketsueki

    Rinsho Ketsueki 59 (7), 899-908, 2018

    The Japanese Society of Hematology

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