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

Park, Gilseung; Burroughs‐Garcia, Jessica; Foster, Clay A.; Hasan, Ameera; Borga, Chiara; Frazer, J. Kimble

doi:10.18632/oncotarget.27555

Cited by 9 publications

(3 citation statements)

References 86 publications

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“…For example, just recently the Frazer group published data on the effectiveness of a known T-ALL steroid, dexamethasone, on fish with B-ALL using the MYC model. The group found the steroid was able to induce remission in 100% of animals, however, after stopping treatment the leukemia returned in 56% of animals (Park et al, 2020).…”

Section: Transgenic Zebrafish Models Of Leukemiamentioning

confidence: 99%

Zebrafish models of acute leukemias: Current models and future directions

Molina

Chavez

Grainger

2020

WIREs Developmental Biology

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Acute myeloid leukemias (AML) and acute lymphoid leukemias (ALL) are heterogenous diseases encompassing a wide array of genetic mutations with both loss and gain of function phenotypes. Ultimately, these both result in the clonal overgrowth of blast cells in the bone marrow, peripheral blood, and other tissues. As a consequence of this, normal hematopoietic stem cell function is severely hampered. Technologies allowing for the early detection of genetic alterations and understanding of these varied molecular pathologies have helped to advance our treatment regimens toward personalized targeted therapies. In spite of this, both AML and ALL continue to be a major cause of morbidity and mortality worldwide, in part because molecular therapies for the plethora of genetic abnormalities have not been developed. This underscores the current need for better model systems for therapy development. This article reviews the current zebrafish models of AML and ALL and discusses how novel gene editing tools can be implemented to generate better models of acute leukemias.

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Section: Transgenic Zebrafish Models Of Leukemiamentioning

confidence: 99%

Zebrafish models of acute leukemias: Current models and future directions

Molina

Chavez

Grainger

2020

WIREs Developmental Biology

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“…A third reporter line, rag2:RFP, labels immature lymphocytes of both the T and B lineages (42). We have also used two newer B cell-specific transgenic reporter lines, cd79a:GFP and cd79b:GFP (30), to analyze B cells and B-ALL (43). Using these five lines, we investigated gross thymic appearance over the first year of life.…”

Section: Thymic Involution Causes Declining Fluorescence In Transgeni...mentioning

confidence: 99%

Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model

Hasan¹,

Macı́as²,

Wood³

et al. 2023

Preprint

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The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self antigens. B cells also reside and develop in the thymus, although their functions are less clear. During thymic involution, a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ~1% of human neonatal thymocytes, but up to ~10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically-manipulatable zebrafish model as a template for involution studies.

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“…In their princeps experiments, Langenau and colleagues [ 121 ] used the rag2 promoter to drive expression of the Myc oncogene and induce T-ALL. However, since B-lymphoblasts also express rag2 and because MYC is known to drive human B-ALL, the Tg(rag2:GFP-Myc) and Tg(rag2:MYC) transgenic zebrafish also develop B-ALL [ 123 , 124 , 125 , 126 ]. While the rag2 gene shows a specific expression in immature lymphoid cells, the zebrafish rag2 promoter used in transgenics is active in both lymphoid and nonlymphoid cell populations including olfactory rosettes, sperm and mesenchymal progenitor cells [ 127 , 128 , 129 ].…”

Section: Transgenesismentioning

confidence: 99%

Genetic Engineering of Zebrafish in Cancer Research

Raby

Völkel

Bourhis

et al. 2020

Cancers

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Zebrafish (Danio rerio) is an excellent model to study a wide diversity of human cancers. In this review, we provide an overview of the genetic and reverse genetic toolbox allowing the generation of zebrafish lines that develop tumors. The large spectrum of genetic tools enables the engineering of zebrafish lines harboring precise genetic alterations found in human patients, the generation of zebrafish carrying somatic or germline inheritable mutations or zebrafish showing conditional expression of the oncogenic mutations. Comparative transcriptomics demonstrate that many of the zebrafish tumors share molecular signatures similar to those found in human cancers. Thus, zebrafish cancer models provide a unique in vivo platform to investigate cancer initiation and progression at the molecular and cellular levels, to identify novel genes involved in tumorigenesis as well as to contemplate new therapeutic strategies.

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

Cited by 9 publications

References 86 publications

Zebrafish models of acute leukemias: Current models and future directions

Zebrafish models of acute leukemias: Current models and future directions

Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model

Genetic Engineering of Zebrafish in Cancer Research

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