JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia

Mansour, Marc R.; He, Shuning; Li, Zhaodong; Lobbardi, Riadh; Abraham, Brian J.; Hug, Clemens; Rahman, Sunniyat; León, Theresa E.; Kuang, Youyi; Zimmerman, Mark W.; Blonquist, Traci M.; Gjini, Evisa; Gutiérrez, Alejandro; Tang, Qin; García-Pérez, Laura; Pike-Overzet, Karin; Anders, Lars; Berezovskaya, Alla; Zhou, Yi; Zon, Leonard I.; Neuberg, Donna; Fielding, Adele K.; Staal, Frank J. T.; Langenau, David M.; Sanda, Takaomi; Young, Richard A.; Look, A. Thomas

doi:10.1084/jem.20170484

Cited by 27 publications

(30 citation statements)

References 73 publications

(105 reference statements)

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“…In the context of pediatric cancer, one of the most valuable aspects of the fish model is the access it provides to a range of developmental time windows and tissue lineages, some only present during early development and absent at the adult stage. Pioneering work modeling T-cell leukemias in fish ( Langenau et al, 2003 ) enabled use of the system to discover novel leukemia genes such as ARID5B ( Leong et al, 2017 ) and JDP2 ( Mansour et al, 2018 ). A transgenic model of neuroblastoma ( Zhu et al, 2012 ) highlighted the role of developmental apoptosis as an oncogene-induced antitumor response.…”

Section: Modeling Developmental Mechanisms Of Childhood Cancermentioning

confidence: 99%

Modeling the developmental origins of pediatric cancer to improve patient outcomes

Amatruda

2021

Disease Models &Amp; Mechanisms

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In the treatment of children and adolescents with cancer, multimodal approaches combining surgery, chemotherapy and radiation can cure most patients, but may cause lifelong health problems in survivors. Current therapies only modestly reflect increased knowledge about the molecular mechanisms of these cancers. Advances in next-generation sequencing have provided unprecedented cataloging of genetic aberrations in tumors, but understanding how these genetic changes drive cellular transformation, and how they can be effectively targeted, will require multidisciplinary collaboration and preclinical models that are truly representative of the in vivo environment. Here, I discuss some of the key challenges in pediatric cancer from my perspective as a physician-scientist, and touch on some promising new approaches that have the potential to transform our understanding of these diseases.

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Section: Modeling Developmental Mechanisms Of Childhood Cancermentioning

confidence: 99%

Modeling the developmental origins of pediatric cancer to improve patient outcomes

Amatruda

2021

Disease Models &Amp; Mechanisms

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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].…”

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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“…As the rag2 promoter is transcriptionally active during the development of T-,cells as well as B-cells, it has recently been shown that B-cell acute lymphoblastic leukemia (B-ALL) could also occur in this zebrafish T-ALL model [95]. Thus far, various zebrafish T-ALL models have been developed based on the constitutive expression of the human intracellular domain of NOTCH1 , mouse Myc [91], mouse Akt2 [92], zebrafish jdp2 [96] and human ARID5B [97] genes. Besides these transgenic zebrafish T-ALL models, Frazer and colleagues identified three zebrafish mutants, Hulk ( hlk ), Shrek ( srk ) and Oscar the grouch ( otg ) that develop transplantable T-ALL using a forward genetic approach [98].…”

Section: Zebrafish As Model System For T-cell Diseasesmentioning

confidence: 99%

Zebrafish and Medaka: Two Teleost Models of T-Cell and Thymic Development

Bajoghli

Dick

Claasen

et al. 2019

IJMS

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Over the past two decades, studies have demonstrated that several features of T-cell and thymic development are conserved from teleosts to mammals. In particular, works using zebrafish (Danio rerio) and medaka (Oryzias latipes) have shed light on the cellular and molecular mechanisms underlying these biological processes. In particular, the ease of noninvasive in vivo imaging of these species enables direct visualization of all events associated with these processes, which are, in mice, technically very demanding. In this review, we focus on defining the similarities and differences between zebrafish and medaka in T-cell development and thymus organogenesis; and highlight their advantages as two complementary model systems for T-cell immunobiology and modeling of human diseases.

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JDP2: An oncogenic bZIP transcription factor in T cell acute lymphoblastic leukemia

Abstract: Mansour et al. demonstrate that JDP2, a bZIP transcription factor, is overexpressed in patients with high-risk T cell acute lymphoblastic leukemia (T-ALL). JDP2 initiates T-ALL in a zebrafish model and leads to steroid resistance in vivo through direct regulation of MCL1.

Cited by 27 publications

References 73 publications

Modeling the developmental origins of pediatric cancer to improve patient outcomes

Modeling the developmental origins of pediatric cancer to improve patient outcomes

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

Zebrafish and Medaka: Two Teleost Models of T-Cell and Thymic Development

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