MYCN Transgenic Zebrafish Model with the Characterization of Acute Myeloid Leukemia and Altered Hematopoiesis

Shen, Lijing; Chen, Fangyuan; Zhang, Yong; Cao, Lanfang; Kong, Ying; Zhong, Min; Wang, Ting

doi:10.1371/journal.pone.0059070

Cited by 34 publications

(27 citation statements)

References 46 publications

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“…These TFs targeted 21 TFBSs that are well-studied hematopoietic regulators, including the Fos/Jun complex [50], Ebox-binding bHLH TFs [51], the GABP complex [52], and retinoic acid receptors [53]. In particular, AP-1 and Egr-1 appeared in all of the models and were targeted by immediate early response genes that are important for apoptosis and differentiation [50] and that are downregulated in ST-HSCs [54].…”

Section: Resultsmentioning

confidence: 99%

Computational Promoter Modeling Identifies the Modes of Transcriptional Regulation in Hematopoietic Stem Cells

Park¹,

Umemoto²,

Saito‐Adachi³

et al. 2014

PLoS ONE

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Extrinsic and intrinsic regulators are responsible for the tight control of hematopoietic stem cells (HSCs), which differentiate into all blood cell lineages. To understand the fundamental basis of HSC biology, we focused on differentially expressed genes (DEGs) in long-term and short-term HSCs, which are closely related in terms of cell development but substantially differ in their stem cell capacity. To analyze the transcriptional regulation of the DEGs identified in the novel transcriptome profiles obtained by our RNA-seq analysis, we developed a computational method to model the linear relationship between gene expression and the features of putative regulatory elements. The transcriptional regulation modes characterized here suggest the importance of transcription factors (TFs) that are expressed at steady state or at low levels. Remarkably, we found that 24 differentially expressed TFs targeting 21 putative TF-binding sites contributed significantly to transcriptional regulation. These TFs tended to be modulated by other nondifferentially expressed TFs, suggesting that HSCs can achieve flexible and rapid responses via the control of nondifferentially expressed TFs through a highly complex regulatory network. Our novel transcriptome profiles and new method are powerful tools for studying the mechanistic basis of cell fate decisions.

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Section: Resultsmentioning

confidence: 99%

Computational Promoter Modeling Identifies the Modes of Transcriptional Regulation in Hematopoietic Stem Cells

Park¹,

Umemoto²,

Saito‐Adachi³

et al. 2014

PLoS ONE

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“…With the successful results of the mouse myeloid leukemia model, the significance of appropriate spatiotemporal expression of the oncogene was confirmed [50]. Although there are many acute myeloid leukemia (AML) zebrafish models [51,52], a CML model using zebrafish has not been reported.…”

Section: Feasibility Of Using Zebrafish As a CML Modelmentioning

confidence: 99%

An overview of chronic myeloid leukemia and its animal models

Chen

et al. 2015

Sci. China Life Sci.

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Chronic myeloid leukemia (CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia (Ph) chromosome or t (9;22) translocation (BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors (TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish (Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML. chronic myeloid leukemia (CML), animal disease model, zebrafish Citation:Ma WX, Ma N, Chen XH, Zhang YY, Zhang WQ. An overview of chronic myeloid leukemia and its animal models.

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“…The NUP98-HOXA9 transgenic fish represents yet another tool for drug discovery and investigation of the pathogenesis of MPN. See Table 2 for details on other zebrafish MPN models [71, 93, 97, 100]. …”

Section: Aml and Other Myeloid Malignanciesmentioning

confidence: 99%

Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights

Harrison

Laroche

Gutiérrez

et al. 2016

Cancer and Zebrafish

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Insights concerning leukemic pathophysiology have been acquired in various animal models and further efforts to understand the mechanisms underlying leukemic treatment resistance and disease relapse promise to improve therapeutic strategies. The zebrafish (Danio rerio) is a vertebrate organism with a conserved hematopoietic program and unique experimental strengths suiting it for the investigation of human leukemia. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of a number of leukemia models. The transparency of the zebrafish when coupled with improved lineage-tracing and imaging techniques has revealed exquisite details of leukemic initiation, progression, and regression. With these advantages, the zebrafish represents a unique experimental system for leukemic research and additionally, advances in zebrafish-based high-throughput drug screening promise to hasten the discovery of novel leukemia therapeutics. To date, investigators have accumulated knowledge of the genetic underpinnings critical to leukemic transformation and treatment resistance and without doubt, zebrafish are rapidly expanding our understanding of disease mechanisms and helping to shape therapeutic strategies for improved outcomes in leukemic patients.

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MYCN Transgenic Zebrafish Model with the Characterization of Acute Myeloid Leukemia and Altered Hematopoiesis

Cited by 34 publications

References 46 publications

Computational Promoter Modeling Identifies the Modes of Transcriptional Regulation in Hematopoietic Stem Cells

Computational Promoter Modeling Identifies the Modes of Transcriptional Regulation in Hematopoietic Stem Cells

An overview of chronic myeloid leukemia and its animal models

Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights

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