The Role of ARID5B in Acute Lymphoblastic Leukemia and Beyond

Wang, Peiqi; Deng, Yun; Yan, Xinyu; Zhu, Jian‐Gang; Yin, Yuan; Shu, Yang; Bai, Dingqun; Zhang, Shouyue; Xu, Hong‐Xi; Lu, Xuanyong

doi:10.3389/fgene.2020.00598

Cited by 27 publications

(17 citation statements)

References 112 publications

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“…3 E). The TF motif mapping shows that the mutation at rs12631656 potentially weakens the binding affinity of ARID5B and SOX13, two known repressors in T cells ( Lefebvre 2010 ; Wang et al 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Enhancer–silencer transitions in the human genome

Huang

Ovcharenko

2022

Genome Res.

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Dual-function regulatory elements (REs), acting as enhancers in some cellular contexts and as silencers in others, have been reported to facilitate the precise gene regulatory response to developmental signals in Drosophila melanogaster. However, with few isolated examples detected, dual-function REs in mammals have yet to be systematically studied. We herein investigated this class of REs in the human genome and profiled their activity across multiple cell types. Focusing on enhancer-silencer transitions specific to the development of T cells, we built an accurate deep learning classifier of regulatory elements and identified about 12,000 silencers active in primary peripheral blood T cells that act as enhancers in embryonic stem cells. As compared to regular silencers, these dual-function REs are evolving under stronger purifying selection and are enriched for mutations associated with disease phenotypes and altered gene expression. In addition, they are enriched in the loci of transcriptional regulators, such as transcription factors (TFs) and chromatin remodeling genes. Dual-function REs consist of two intertwined but largely distinct sets of binding sites bound by either activating or repressing TFs - depending on the type of RE function in a given cell line. This indicates the recruitment of different TFs for different regulatory modes and a complex DNA sequence composition of these REs with dual activating and repressive encoding. With an estimated over 6% of cell type-specific human silencers acting as dual-function REs, this overlooked class of REs requires a specific investigation on how their inherent functional plasticity might be a contributing factor to human diseases.

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Section: Resultsmentioning

confidence: 99%

Enhancer–silencer transitions in the human genome

Huang

Ovcharenko

2022

Genome Res.

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“…The protein is widely expressed in most tissue types [ 56 ] and is associated with adipogenesis and liver development. It mainly serves as a transcriptional modulator and regulates targeted gene expression by recruiting PHD finger protein 2 [ 82 ]. This gene is also involved in cell growth and differentiation of B-lymphocyte progenitors, and is associated with the incident and relapse of ALL.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Taylor

Vang

López-López

et al. 2021

Cancers

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Methotrexate (MTX) is a mainstay therapeutic agent administered at high doses for the treatment of pediatric and adult malignancies, such as acute lymphoblastic leukemia, osteosarcoma, and lymphoma. Despite the vast evidence for clinical efficacy, high-dose MTX displays significant inter-individual pharmacokinetic variability. Delayed MTX clearance can lead to prolonged, elevated exposure, causing increased risks for nephrotoxicity, mucositis, seizures, and neutropenia. Numerous pharmacogenetic studies have investigated the effects of several genes and polymorphisms on MTX clearance in an attempt to better understand the pharmacokinetic variability and improve patient outcomes. To date, several genes and polymorphisms that affect MTX clearance have been identified. However, evidence for select genes have conflicting results or lack the necessary replication and validation needed to confirm their effects on MTX clearance. Therefore, we performed a systematic review to identify and then summarize the pharmacogenetic factors that influence high-dose MTX pharmacokinetics in pediatric malignancies. Using the PRISMA guidelines, we analyzed 58 articles and 24 different genes that were associated with transporter pharmacology or the folate transport pathway. We conclude that there is only one gene that reliably demonstrates an effect on MTX pharmacokinetics: SLCO1B1.

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“…The expression of ARIEL is associated with the ARID5B enhancer activity and is required for the recruitment of the Mediator complex toward the ARID5B promoter and thereby increasing the expression of this transcription factor. ARID5B is necessary to activate the TAL1-induced transcriptional program and the MYC oncogene [ 121 ]. Curiously, TAL1 positively modulates ARIEL expression, showing a feedback regulatory system.…”

Section: Transcriptional Gene Modulation By Lncrnasmentioning

confidence: 99%

Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

García-Padilla

Dueñas

García‐López

et al. 2022

IJMS

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Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

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The Role of ARID5B in Acute Lymphoblastic Leukemia and Beyond

Cited by 27 publications

References 112 publications

Enhancer–silencer transitions in the human genome

Enhancer–silencer transitions in the human genome

Systematic Review of Pharmacogenetic Factors That Influence High-Dose Methotrexate Pharmacokinetics in Pediatric Malignancies

Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

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