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zebrafish leukemia

Adam P Deveau, Victoria L Bentley, Jason N Berman
Current treatment strategies for acute leukemias largely rely on nonspecific cytotoxic drugs that result in high therapy-related morbidity and mortality. Cost effective, pertinent animal models are needed to link in vitro studies with the development of new therapeutic agents in clinical trials on a high-throughput scale. However, targeted therapies have had limited success moving from bench-to-clinic, often due to unexpected off-target effects. The zebrafish has emerged as a reliable in vivo tool for modeling human leukemia...
October 6, 2016: Experimental Hematology
Kou-Ray Lin, Hsin-Fang Yang-Yen, Huang-Wei Lien, Wei-Hao Liao, Chang-Jen Huang, Liang-In Lin, Chung-Leung Li, Jeffrey Jong-Young Yen
Tribbles homolog 2 (Trib2) is a member of Tribbles protein pseudokinases and involves in apoptosis, autoimmunity, cancer, leukemia and erythropoiesis, however, the physiological function of Trib2 in hematopoietic system remains to be elucidated. Here, we report that Trib2 knockout (KO) mice manifest macrocytic anemia and increase of T lymphocytes. Although Trib2 deficient RBCs have similar half-life as the control RBCs, Trib2 KO mice are highly vulnerable to oxidant-induced hemolysis. Endogenous Trib2 mRNA is expressed in early hematopoietic progenitors, erythroid precursors, and lymphoid lineages, but not in mature RBCs, myeloid progenitors and granulocytes...
2016: Scientific Reports
Elisa Barbieri, Gianluca Deflorian, Federica Pezzimenti, Debora Valli, Marco Saia, Natalia Meani, Alicja M Gruszka, Myriam Alcalay
Nucleophosmin (NPM1) is a ubiquitous multifunctional phosphoprotein with both oncogenic and tumor suppressor functions. Mutations of the NPM1 gene are the most frequent genetic alterations in acute myeloid leukemia (AML) and result in the expression of a mutant protein with aberrant cytoplasmic localization, NPMc+. Although NPMc+ causes myeloproliferation and AML in animal models, its mechanism of action remains largely unknown. Here we report that NPMc+ activates canonical Wnt signaling during the early phases of zebrafish development and determines a Wnt-dependent increase in the number of progenitor cells during primitive hematopoiesis...
July 28, 2016: Oncotarget
Vinothkumar Rajan, Graham Dellaire, Jason N Berman
The zebrafish is a widely accepted model to study leukemia. The major advantage of studying leukemogenesis in zebrafish is attributed to its short life cycle and superior imaging capacity. This chapter highlights using transgenic- and xenograft-based models in zebrafish to study a specific leukemogenic mutation and analyze therapeutic responses in vivo.
2016: Methods in Molecular Biology
W Liu, M Wu, Z Huang, J Lian, J Chen, T Wang, A Y H Leung, Y Liao, Z Zhang, Q Liu, K Yen, S Lin, L I Zon, Z Wen, Y Zhang, W Zhang
The c-MYB transcription factor is a key regulator of hematopoietic cell proliferation and differentiation, and dysregulation of c-MYB activity often associates with various hematological disorders. Yet, its pathogenic role remains largely unknown due to lack of suitable animal models. Here, we report a detail characterization of a c-myb-gfp transgenic zebrafish harboring c-Myb hyperactivity (named c-myb(hyper)). This line exhibits abnormal granulocyte expansion that resembles human myelodysplastic syndrome (MDS) from embryonic stage to adulthood...
July 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jing Tian, Ziwei Li, Yang Han, Tao Jiang, Xiaoming Song, Guosheng Jiang
Early growth response gene-1 (EGR1) widely exists in the cell nucleus of such as, zebrafish, mice, chimpanzees and humans, an it also can be observed in the cytoplasm of some tumors. EGR1 was named just after its brief and rapid expression of different stimuli. Accumulating studies have extensively demonstrated that the widespread dysregulation of EGR1 is involved in hematological malignancies such as human acute myeloid leukemia (AML), chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B cell lymphoma...
May 2016: Intractable & Rare Diseases Research
Nicholas R Harrison, Fabrice J F Laroche, Alejandro Gutierrez, Hui Feng
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...
2016: Advances in Experimental Medicine and Biology
Xiaoqian Huang, Ira Agrawal, Zhen Li, Weiling Zheng, Qingsong Lin, Zhiyuan Gong
The past decade has witnessed a remarkable advancement of the zebrafish model in cancer research. With the rapid development of genomic tools, it is increasingly feasible to perform genome-wide analyses to identify changes associated with cancer in a wide array of model organisms. These genomic tools, particularly transcriptomic analyses using DNA microarray and RNA sequencing platforms, have now become widely used in zebrafish cancer models to uncover novel biology and common molecular pathways underlying hepatocellular carcinoma, intrahepatic cholangiocarcinoma, melanoma, embryonal rhabdomyosarcoma (ERMS), T cell acute lymphoblastic leukemia (T-ALL), Ewing's sarcoma and glioma...
2016: Advances in Experimental Medicine and Biology
Finola E Moore, Elaine G Garcia, Riadh Lobbardi, Esha Jain, Qin Tang, John C Moore, Mauricio Cortes, Aleksey Molodtsov, Melissa Kasheta, Christina C Luo, Amaris J Garcia, Ravi Mylvaganam, Jeffrey A Yoder, Jessica S Blackburn, Ruslan I Sadreyev, Craig J Ceol, Trista E North, David M Langenau
Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages...
May 30, 2016: Journal of Experimental Medicine
C Tregnago, E Manara, M Zampini, V Bisio, C Borga, S Bresolin, S Aveic, G Germano, G Basso, M Pigazzi
cAMP response element binding protein (CREB) is frequently overexpressed in acute myeloid leukemia (AML) and acts as a proto-oncogene; however, it is still debated whether such overactivation alone is able to induce leukemia as its pathogenetic downstream signaling is still unclear. We generated a zebrafish model overexpressing CREB in the myeloid lineage, which showed an aberrant regulation of primitive hematopoiesis, and in 79% of adult CREB-zebrafish a block of myeloid differentiation, triggering to a monocytic leukemia akin the human counterpart...
September 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Guruchandar Arulmozhivarman, Martin Stöter, Marc Bickle, Martin Kräter, Manja Wobus, Gerhard Ehninger, Friedrich Stölzel, Michael Brand, Martin Bornhäuser, Nona Shayegi
Hematopoietic stem and progenitor cells (HSPCs) generate all cell types of the blood and are crucial for homeostasis of all blood lineages in vertebrates. Hematopoietic stem cell transplantation (HSCT) is a rapidly evolving technique that offers potential cure for hematologic cancers, such as leukemia or lymphoma. HSCT may be autologous or allogenic. Successful HSCT depends critically on the abundance of engraftment-competent HSPCs, which are currently difficult to obtain in large numbers. Therefore, finding compounds that enhance either the number or the activity of HSPCs could improve prognosis for patients undergoing HSCT and is of great clinical interest...
October 2016: Journal of Biomolecular Screening
Xin-Ying Zhou, Ting Zhang, Long Ren, Jun-Jie Wu, Weimin Wang, Jing-Xia Liu
Copper, as an essential trace mineral, can cause diseases such as childhood leukemia at excess levels, but has been applied in anemia therapy for a long time. However, few reports have studied its role during hematopoiesis at the molecular level in an animal model. In this study, by microarray, qRT-PCR, whole-mount in situ hybridization and O-dianisidine staining detections, we revealed the increased expression of hemoglobin in copper-exposed embryos. Secondly, we found that copper-exposed embryos exhibited high levels of reactive oxygen species (ROS), and genes in oxygen binding and oxygen transporting were up-regulated in the embryos...
June 2016: Aquatic Toxicology
Supriya Borah, Praveen Barrodia, Rajeeb K Swain
The nucleolar protein 4-like (NOL4L) gene is present on chromosome 20 (20q11.21) in humans. Parts of this gene have been shown to fuse with RUNX1 and PAX5 in acute myeloid leukemia and acute lymphoblastic leukemia, respectively. The normal function of NOL4L in humans and other organisms is not well understood. The expression patterns and functions of NOL4L homologs during vertebrate development have not been reported. We sought to address these questions by studying the expression pattern of zebrafish nol4l during embryogenesis...
2016: International Journal of Developmental Biology
N M Anderson, D Li, H L Peng, F J F Laroche, M R Mansour, E Gjini, M Aioub, D J Helman, J E Roderick, T Cheng, I Harrold, Y Samaha, L Meng, A Amsterdam, D S Neuberg, T T Denton, T Sanda, M A Kelliher, A Singh, A T Look, H Feng
Despite the pivotal role of MYC in the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and many other cancers, the mechanisms underlying MYC-mediated tumorigenesis remain inadequately understood. Here we utilized a well-characterized zebrafish model of Myc-induced T-ALL for genetic studies to identify novel genes contributing to disease onset. We found that heterozygous inactivation of a tricarboxylic acid (TCA) cycle enzyme, dihydrolipoamide S-succinyltransferase (Dlst), significantly delayed tumor onset in zebrafish without detectable effects on fish development...
June 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Li-Ping Shu, Zhi-Wei Zhou, Ting Zhou, Min Deng, Mei Dong, Yi Chen, Yan-Fang Fu, Yi Jin, Shu-Feng Zhou, Zhi-Xu He
Hemangioblast, including primitive hematopoietic progenitor cells, play an important role in hematopoietic development, however, the underlying mechanism for the propagation of hematopoietic progenitor cells remains elusive. A variety of regulatory molecules activated in early embryonic development play a critical role in the maintenance of function of hematopoietic progenitor cells. Homeobox transcription factors are an important class of early embryonic developmental regulators determining hematopoietic development...
December 2015: Clinical and Experimental Pharmacology & Physiology
Alessandro Morotti, Cristina Panuzzo, Sabrina Crivellaro, Giovanna Carrà, Davide Torti, Angelo Guerrasio, Giuseppe Saglio
PTEN deletion in the mouse and in the zebrafish highlights the essential role of this tumor suppressor in the development of myeloid malignancies, in particular acute myeloid leukemia and myeloproliferative disorders. In humans, extensive genetic sequences of myeloid malignancies did not reveal recurrent PTEN mutations and deletions. However, PTEN was shown to be functionally inactivated in several acute myeloid leukemia and chronic myeloid leukemia samples, through both post-trasductional modifications, changes in protein levels and cellular compartmentalization...
November 23, 2015: Hematology Reports
E Aleksejeva, A Houel, V Briolat, J-P Levraud, C Langevin, P Boudinot
The BTB-POZ transcription factor Promyelocytic Leukemia Zinc Finger (PLZF, or ZBTB16) has been recently identified as a major factor regulating the induction of a subset of Interferon stimulated genes in human and mouse. We show that the two co-orthologues of PLZF found in zebrafish show distinct expression patterns, especially in larvae. Although zbtb16a/plzfa and zbtb16b/plzfb are not modulated by IFN produced during viral infection, their over-expression increases the level of the early type I IFN response, at a critical phase in the race between the virus and the host response...
April 2016: Developmental and Comparative Immunology
Lijing Shen, Jianyi Zhu, Fangyuan Chen, Wenjie Lin, Jiayi Cai, Jihua Zhong, Hua Zhong
BACKGROUND: Acute myeloid leukemia (AML) 1-Evi-1 is a chimeric gene generated by the t (3; 21) (q26; q22) translocation, which leads into malignant transformation of hematopoietic stem cells by unclear mechanisms. This in vivo study aimed to establish a stable line of zebrafish expressing the human RUNX1-Evi-1 fusion gene under the control of a heat stress-inducible bidirectional promoter, and investigate its roles in hematopoiesis and hematologic malignancies. METHODS: We introduced human RUNX1-Evi-1 fusion gene into embryonic zebrafish through a heat-shock promoter to establish Tg(RE:HSE:EGFP) zebrafish...
2015: BMC Cancer
Jing Xu, Xiumei Zhu, Liyan Qiu
The conventional chemotherapeutic agent doxorubicin hydrochloride (DOX·HCl) is often accompanied by drug resistance which has severely hindered its clinical application. By taking advantage of the self-assembled behavior of amphiphilic polyphosphazenes, we constructed novel polymersomes loading DOX·HCl or desalted DOX with chloroquine phosphate (CQ) as a drug resistance-reversal agent at 1:1 or 2:1 weight ratios via a one-step common dialysis method. The cytotoxicity evaluation of this dual drug-loaded polymersome was performed on DOX-resistant MCF-7/Adr breast cancer and HL60/Adr leukemia cells...
February 10, 2016: International Journal of Pharmaceutics
WeiXu Ma, Ning Ma, XiaoHui Chen, YiYue Zhang, WenQing Zhang
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...
December 2015: Science China. Life Sciences
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