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Cancer and Zebrafish pp 335–369Cite as

Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 916))

Abstract

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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Abbreviations

4HT:

4-hydroxytamoxifen

ALL:

Acute lymphoblastic leukemia

AML:

Acute myeloid leukemia

B-ALL:

B-cell acute lymphoblastic leukemia

CLL:

Chronic lymphocytic leukemia

CML:

Chronic myeloid leukemia

CRISPR/Cas9:

Clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9

dpf:

Days post fertilization

EGFP:

Enhanced green fluorescent protein

ENU:

N-ethyl-N-nitrosourea

GFP:

Green fluorescent protein

GMP:

Granulocyte/macrophage progenitors

HOXA9:

Homeobox A9

HSCs:

Hematopoietic stem cells

HSCT:

Hematopoietic stem cell transplantation

ICN1:

Intracellular portion of human NOTCH1

LED:

Light emitting diode

LP:

Lymphoid progenitor (cells)

LPC:

Leukemia-propagating cells

LSCM:

Laser scanning fluorescent confocal microscopy

MDS:

Myelodysplastic syndrome

MEP:

Megakaryocyte-erythrocyte progenitors

MP:

Myeloid progenitor (cells)

MPN:

Myeloproliferative neoplasm

NUP98:

Nucleoporin 98 kDa

PP2A:

Protein phosphatase 2

Pro-B:

Pro-B-lymphocytes

Pro-T:

Pro-T-lymphocytes

RFP:

Red fluorescent protein

S1P1:

Singhosine-1 phosphate receptor 1

SDCM:

Spinning disc confocal microscopy

TALENs:

Transcription activator-like effector nucleases

T-ALL:

T-cell acute lymphoblastic leukemia

TET2:

Tet methylcytosine dioxygenase 2

TILLING:

Targeting induced local lesions IN Genomes

T-LBL:

T-cell acute lymphoblastic lymphoma

ZFNs:

Zinc finger nucleases

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Acknowledgements

The authors thank Joseph Hirsch for editorial assistance, and Leah Huiting and Dr. Nicole M. Anderson for helpful comments and suggestions. N.R.H is supported by a training grant (T32GM008541) from the National Institutes of Health. H.F. is supported by a grant (R00CA134743) from the National Institutes of Health, a career development grant from the St. Baldrick’s Foundation, a Karin Grunebaum Faculty Fellowship from the Karin Grunebaum Cancer Foundation, a Ralph Edwards Career Development Professorship from Boston University, and an institutional grant (IRG −72-001-36-IRG) from the American Cancer Society.

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    1. Department of Pharmacology and Experimental Therapeutics, Cancer Research Center, Section of Hematology and Medical Oncology, Boston University School of Medicine, Boston, MA, USA

      Nicholas R. Harrison, Fabrice J. F. Laroche & Hui Feng

    2. Division of Hematology, Boston Children’s Hospital, Boston, MA, USA

      Alejandro Gutierrez

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      David M. Langenau

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    Harrison, N.R., Laroche, F.J.F., Gutierrez, A., Feng, H. (2016). Zebrafish Models of Human Leukemia: Technological Advances and Mechanistic Insights. In: Langenau, D. (eds) Cancer and Zebrafish. Advances in Experimental Medicine and Biology, vol 916. Springer, Cham. https://doi.org/10.1007/978-3-319-30654-4_15

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