Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia

Tan, Tze King; Zhang, Chujing; Sanda, Takaomi

doi:10.1007/s12185-018-2518-z

Cited by 27 publications

(27 citation statements)

References 141 publications

(216 reference statements)

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“…For example, the genetic looping interactions are known to be associated with the expression of ARID5B (Studd et al, 2017). ARID5B may serve as a transcriptional activator that enhances the regulatory network triggered by the TAL1 complex in T-ALL cell proliferation (Tan, Zhang & Sanda, 2019). In recent years, studies showed that the mutations and single nucleotide polymorphisms of TF, ARID5B are involved in the oncogenesis of ALL.…”

Section: Discussionmentioning

confidence: 99%

Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia

Wee

Liu

Zhao

2021

PeerJ

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Background Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. It can be caused by mutations that turn on oncogenes or turn off tumour suppressor genes. For instance, changes in certain genes including Rb and p53 are common in ALL cells. Oncogenes and TSGs may serve as a modulator gene to regulate the gene expression level via their respective target genes. To investigate the regulatory relationship between oncogenes, tumour suppressor genes and transcription factors at the post translational level in childhood ALL, we performed an integrative network analysis on the gene regulation in the post-translational level for childhood ALL based on many publicly available cancer gene expression data including TARGET and GEO database. Methods We collected 259 childhood ALL-related genes from the latest online leukemia database, Leukemia Gene Literature Database. These 259 genes were selected from a comprehensive systematic literature with experimental evidences. The identified and curated genes were also associated with patient survival cases and we incorporated this pediatric ALL-related gene list into our analysis. We extracted the known human TFs from the TRRUST database. Among 259 childhood ALL-related genes, 101 unique regulators were mapped to the list of oncogene and tumour suppressor genes (TSGs) from the ONGene and the TSGene databases, and these included 74 TSGs, 62 oncogenes and 46 TF genes. Results The resulted regulation was presented as a hierarchical regulatory network with transcription factors (TFs) as intermediate regulators connecting the top modulators (oncogene and TSGs) to the common target genes. Cross-validation was applied to the results from the TARGET dataset by identifying the consistent regulatory motifs based on three independent ALL expression datasets. A three-layer regulatory network of consistent positive modulators in childhood ALL was constructed in which 74 modulators (40 oncogenes, 34 TSGs) are considered as the most important regulators. The middle layer and the bottom layer contain 34 TFs and 176 target genes, respectively. Oncogenes mostly participated in positive regulation of gene expression and the transcription process of RNA II polymerase, while TSGs were mainly involved in the negative regulation of gene expression. In addition, the oncogene-specific targets were enriched with regulators of the MAPK cascade while tumour suppressor-specific targets were associated with cell death. Conclusion The results revealed that oncogenes and TSGs possess a different functional regulatory pattern with regard to not only their biological functions but also their specific target genes in childhood ALL cancer progression. Taken together, our findings could contribute to a better understanding of the important regulatory mechanisms and this method could be used to analyse the targeted genes at the post-translational level in childhood ALL through integrative network analysis.

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Section: Discussionmentioning

confidence: 99%

Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia

Wee

Liu

Zhao

2021

PeerJ

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“…The TAL1 gene is an essential transcriptional regulator of hematopoiesis, in particular for the specification of hematopoietic lineages [39]. TAL1 is also implicated as a key transcriptional factor involved in the development of T-cell acute lymphoblastic leukemia [40]. Similarly, the MLLT3 (mixed lineage leukemia, translocated to 3, also known as AF9) gene is a critical regulator of hematopoietic stem cell self-renewal, and also implicated in leukemias [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

Wang

Yekula

Muralidharan

et al. 2020

Cancers

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Sequencing studies have provided novel insights into the heterogeneous molecular landscape of glioblastoma (GBM), unveiling a subset of patients with gene fusions. Tissue biopsy is highly invasive, limited by sampling frequency and incompletely representative of intra-tumor heterogeneity. Extracellular vesicle-based liquid biopsy provides a minimally invasive alternative to diagnose and monitor tumor-specific molecular aberrations in patient biofluids. Here, we used targeted RNA sequencing to screen GBM tissue and the matched plasma of patients (n = 9) for RNA fusion transcripts. We identified two novel fusion transcripts in GBM tissue and five novel fusions in the matched plasma of GBM patients. The fusion transcripts FGFR3-TACC3 and VTI1A-TCF7L2 were detected in both tissue and matched plasma. A longitudinal follow-up of a GBM patient with a FGFR3-TACC3 positive glioma revealed the potential of monitoring RNA fusions in plasma. In summary, we report a sensitive RNA-seq-based liquid biopsy strategy to detect RNA level fusion status in the plasma of GBM patients.

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“…TAL1/SCL is considered as a master TF delineating the cell fate and the identity of progenitor and normal hematopoietic stem cells (HSCs). It regulates other hematopoietic TFs thus has a potential for cell reprogramming [22]. TAL1 also binds CBP/p300 acetyltransferase [61,62].…”

Section: The Role Of the Bhlh Proteins In Transcriptionmentioning

confidence: 99%

The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors

Tarczewska

Greb‐Markiewicz

2019

IJMS

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The bHLH proteins are a family of eukaryotic transcription factors regulating expression of a wide range of genes involved in cell differentiation and development. They contain the Helix-Loop-Helix (HLH) domain, preceded by a stretch of basic residues, which are responsible for dimerization and binding to E-box sequences. In addition to the well-preserved DNA-binding bHLH domain, these proteins may contain various additional domains determining the specificity of performed transcriptional regulation. According to this, the family has been divided into distinct classes. Our aim was to emphasize the significance of existing disordered regions within the bHLH transcription factors for their functionality. Flexible, intrinsically disordered regions containing various motives and specific sequences allow for multiple interactions with transcription co-regulators. Also, based on in silico analysis and previous studies, we hypothesize that the bHLH proteins have a general ability to undergo spontaneous phase separation, forming or participating into liquid condensates which constitute functional centers involved in transcription regulation. We shortly introduce recent findings on the crucial role of the thermodynamically liquid-liquid driven phase separation in transcription regulation by disordered regions of regulatory proteins. We believe that further experimental studies should be performed in this field for better understanding of the mechanism of gene expression regulation (among others regarding oncogenes) by important and linked to many diseases the bHLH transcription factors.

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Oncogenic transcriptional program driven by TAL1 in T-cell acute lymphoblastic leukemia

Cited by 27 publications

References 141 publications

Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia

Identification of consistent post-translational regulatory triplets related to oncogenic and tumour suppressive modulators in childhood acute lymphoblastic leukemia

Novel Gene Fusions in Glioblastoma Tumor Tissue and Matched Patient Plasma

The Significance of the Intrinsically Disordered Regions for the Functions of the bHLH Transcription Factors

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