Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia

Liau, Wei-Siang; Tan, Shi Hao; Ngoc, Phuong Cao Thi; Wang, Chelsia Qiuxia; Tergaonkar, Vinay; Feng, Hui; Gong, Zhiyuan; Osato, Motomi; Look, A. Thomas; Sanda, Takaomi

doi:10.1038/leu.2016.392

Cited by 36 publications

(41 citation statements)

References 58 publications

(84 reference statements)

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“…The microarray gene expression data set for T-ALL cell lines was reported previously by us (Liau et al 2017) and has been deposited under accession number GSE90138. The microarray data set for primary T-ALL cases has been reported under accession number GSE26713 (Homminga et al 2011) and was analyzed with R2 (http://r2.amc.nl).…”

Section: Public Microarray and Rna-seq Data Setsmentioning

confidence: 99%

ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis

et al. 2017

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The oncogenic transcription factor induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified () as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells. The enhancer located 135 kb upstream of the gene locus is activated under a superenhancer in T-ALL cells but not in normal T cells. Notably, ARID5B-bound regions are associated predominantly with active transcription. ARID5B and TAL1 frequently co-occupy target genes and coordinately control their expression. ARID5B positively regulates the expression of TAL1 and its regulatory partners. ARID5B also activates the expression of the oncogene Importantly, ARID5B is required for the survival and growth of T-ALL cells and forced expression of ARID5B in immature thymocytes results in thymus retention, differentiation arrest, radioresistance, and tumor formation in zebrafish. Our results indicate that ARID5B reinforces the oncogenic transcriptional program by positively regulating the TAL1-induced regulatory circuit and in T-ALL, thereby contributing to T-cell leukemogenesis.

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Section: Public Microarray and Rna-seq Data Setsmentioning

confidence: 99%

ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis

et al. 2017

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“…myeloid leukemia (AML) and T-ALL [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. For T-ALL in particular, zebrafish models have been highly informative, advancing our understanding of T-ALL genetics, pro-and anti-oncogenic interactions between different genes and pathways, tumor heterogeneity, leukemia stem cells, and in screens for new therapeutics [28,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53]. However, despite the fact that zebrafish T-ALL models had proven to be fertile grounds for study, B-ALL modeling in D. rerio had not been fruitful, with only one low penetrance and long latency line reported [54].…”

Section: Research Perspectivementioning

confidence: 99%

Zebrafish B cell acute lymphoblastic leukemia: new findings in an old model

et al. 2020

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Acute lymphoblastic leukemia (ALL) is the most common pediatric, and ninth most common adult, cancer. ALL can develop in either B or T lymphocytes, but B-lineage ALL (B-ALL) exceeds TALL clinically. As for other cancers, animal models allow study of the molecular mechanisms driving ALL. Several zebrafish (Danio rerio) TALL models have been reported, but until recently, robust D. rerio BALL models were not described. Then, D. rerio BALL was discovered in two related zebrafish transgenic lines; both were already known to develop TALL. Here, we report new BALL findings in one of these models, fish expressing transgenic human MYC (hMYC). We describe BALL incidence in a large cohort of hMYC fish, and show BALL in two new lines where TALL does not interfere with BALL detection. We also demonstrate BALL responses to steroid and radiation treatments, which effect ALL remissions, but are usually followed by prompt relapses. Finally, we report gene expression in zebrafish B lymphocytes and BALL , in both bulk samples and single Band TALL cells. Using these gene expression profiles, we compare differences between the two new D. rerio BALL models, which are both driven by transgenic mammalian MYC oncoproteins. Collectively, these new data expand the utility of this new vertebrate BALL model.

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“…The other example of TAL1 targets in T-ALL cells is the GIMAP gene cluster [128], which consists of seven genes (GIMAP1, GIMAP2, GIMAP4, GIMAP5, GIMAP6, GIMAP7 and GIMAP8) that belong to the same gene family. Some of the GIMAP genes have been implicated in the T-cell survival-death decision [129]; however, their molecular functions have not been elucidated yet.…”

Section: Other Tal1 Target Genesmentioning

confidence: 99%

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

2018

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TAL1/SCL is a prime example of an oncogenic transcription factor that is abnormally expressed in acute leukemia due to the replacement of regulator elements. This gene has also been recognized as an essential regulator of hematopoiesis. TAL1 expression is strictly regulated in a lineage- and stage-specific manner. Such precise control is crucial for the switching of the transcriptional program. The misexpression of TAL1 in immature thymocytes leads to a widespread series of orchestrated downstream events that affect several different cellular machineries, resulting in a lethal consequence, namely T-cell acute lymphoblastic leukemia (T-ALL). In this article, we will discuss the transcriptional regulatory network and downstream target genes, including protein-coding genes and non-coding RNAs, controlled by TAL1 in normal hematopoiesis and T-cell leukemogenesis.

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Aberrant activation of the GIMAP enhancer by oncogenic transcription factors in T-cell acute lymphoblastic leukemia

Cited by 36 publications

References 58 publications

ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis

ARID5B as a critical downstream target of the TAL1 complex that activates the oncogenic transcriptional program and promotes T-cell leukemogenesis

Zebrafish B cell acute lymphoblastic leukemia: new findings in an old model

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

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