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zebrafish leukemia

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https://www.readbyqxmd.com/read/28335858/netting-novel-regulators-of-hematopoiesis-and-hematologic-malignancies-in-zebrafish
#1
Wanda Kwan, Trista E North
Zebrafish are one of the preeminent model systems for the study of blood development (hematopoiesis), hematopoietic stem and progenitor cell (HSPC) biology, and hematopathology. The zebrafish hematopoietic system shares strong similarities in functional populations, genetic regulators, and niche interactions with its mammalian counterparts. These evolutionarily conserved characteristics, together with emerging technologies in live imaging, compound screening, and genetic manipulation, have been employed to successfully identify and interrogate novel regulatory mechanisms and molecular pathways that guide hematopoiesis...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28245372/-establishment-of-a-xenografted-acute-myeloid-leukemia-model-by-using-zebrafish
#2
Yong-Bin Ye, Ming-Wan Zhang, Da-Fa Qiu, Zi-Wen Guo, Hui-Qing He, Xiao-Jun Xu
Objectve: To investigate the feasibility of establishing xenografted leukemia model by zebrafish, so as to provide the more direct model in vitro and experimental evidence for study of acute myeloid leukemia and screening of the drugs for targeting therapy. METHODS: Acute myeloid leukemia cell line KG-1a was labeled with red fluorescent dye-MitoRed, then the labeled cells were injected into the yolk sac of zebrafish embryos. Morphological observation, cell count and histopathological detection were used to analyse the infiltration and metastasis of KG-1a cells in zebrafish...
February 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28129858/zebrafish-models-of-leukemia
#3
S He, C-B Jing, A T Look
The zebrafish, Danio rerio, is a well-established, invaluable model system for the study of human cancers. The genetic pathways that drive oncogenesis are highly conserved between zebrafish and humans, and multiple unique attributes of the zebrafish make it a tractable tool for analyzing the underlying cellular processes that give rise to human disease. In particular, the high conservation between human and zebrafish hematopoiesis (Jing & Zon, 2011) has stimulated the development of zebrafish models for human hematopoietic malignancies to elucidate molecular pathogenesis and to expedite the preclinical investigation of novel therapies...
2017: Methods in Cell Biology
https://www.readbyqxmd.com/read/28075592/total-syntheses-and-biological-activities-of-vinylamycin-analogues
#4
Jinghan Wang, Beijia Kuang, Xiaoqian Guo, Jianwei Liu, Yahui Ding, Jiangnan Li, Shende Jiang, Ying Liu, Fang Bai, Luyuan Li, Quan Zhang, Xiao-Yu Zhu, Bo Xia, Chun-Qi Li, Liang Wang, Guang Yang, Yue Chen
Natural depsipeptide vinylamycin was reported to be an antibiotic previously. Herein we report vinylamycin to be active against K562 leukemia cells (IC50 = 4.86 μM) and be unstable in plasma (t1/2 = 0.54 h). A total of 24 vinylamycin analogues with modification of the OH group and chiral centers were generated via a combinatorial approach. The lead compound 1a was subsequently characterized as having the following: no antimicrobial activity, significantly higher plasma stability (t1/2 = 14.3 h), improved activity against K562 leukemia cells (IC50 = 0...
February 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28043811/honokiol-induces-proteasomal-degradation-of-aml1-eto-oncoprotein-via-increasing-ubiquitin-conjugase-ubch8-expression-in-leukemia
#5
Bin Zhou, Haiying Li, Chongyun Xing, Haige Ye, Jianhua Feng, Jianbo Wu, Zhongqiu Lu, Jing Fang, Shenmeng Gao
AML1-ETO is the most common oncoprotein leading to acute myeloid leukemia (AML), in which 5-year survival rate is only about 30%. However, currently there are no specific therapies for AML patients with AML1-ETO. Here, we report that AML1-ETO protein is rapidly degraded by Honokiol (HNK), a natural phenolic compound isolated from the plant Magnolia officinalis. HNK induced the degradation of AML1-ETO in a concentration- and time-dependent manner in leukemic cell lines and primary AML blasts with t(8;21) translocation...
December 30, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28028313/aberrant-activation-of-the-gimap-enhancer-by-oncogenic-transcription-factors-in-t-cell-acute-lymphoblastic-leukemia
#6
W S Liau, S H Tan, P C T Ngoc, C Q Wang, V Tergaonkar, H Feng, Z Gong, M Osato, A T Look, T Sanda
The transcription factor TAL1/SCL is one of the most prevalent oncogenes in T-cell acute lymphoblastic leukemia (T-ALL), a malignant disorder resulting from leukemic transformation of thymus T-cell precursors. TAL1 is normally expressed in hematopoietic stem cells (HSCs) but is silenced in immature thymocytes. We hypothesize that TAL1 contributes to leukemogenesis by activating genes that are normally repressed in immature thymocytes. Herein, we identified a novel TAL1-regulated super-enhancer controlling the GIMAP locus, which resides within an insulated chromosomal locus in T-ALL cells...
January 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27827822/ndrg1b-and-fam49ab-modulate-the-pten-pathway-to-control-t-cell-lymphopoiesis-in-the-zebrafish
#7
Roman A Li, David Traver, Thomas Matthes, Julien Y Bertrand
During hematopoiesis, the balance between proliferation, differentiation, and apoptosis is tightly regulated in order to maintain homeostasis. Failure in these processes can ultimately lead to uncontrolled proliferation and leukemia. Phosphatase and tensin homolog (PTEN) is one of the molecular pathways involved in this balance. By opposing PI3-kinases, PTEN inhibits proliferation and promotes differentiation and is thus considered a tumor suppressor. Indeed, PTEN is frequently mutated in many cancers, including leukemias...
December 29, 2016: Blood
https://www.readbyqxmd.com/read/27811851/establishment-of-a-congenital-amegakaryocytic-thrombocytopenia-model-and-a-thrombocyte-specific-reporter-line-in-zebrafish
#8
Q Lin, Y Zhang, R Zhou, Y Zheng, L Zhao, M Huang, X Zhang, A Y H Leung, W Zhang, Y Zhang
Mutations in the human myeloproliferative leukemia protein gene (MPL) are known to cause congenital amegakaryocytic thrombocytopenia (CAMT). The prognosis of this heritable disorder is poor and bone marrow transplantation is the only effective treatment. Here, by using transcription activator-like effect or nucleases (TALEN) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl leaded to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult HSPCs...
November 4, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27810924/single-cell-imaging-of-normal-and-malignant-cell-engraftment-into-optically-clear-prkdc-null-scid-zebrafish
#9
John C Moore, Qin Tang, Nora Torres Yordán, Finola E Moore, Elaine G Garcia, Riadh Lobbardi, Ashwin Ramakrishnan, Dieuwke L Marvin, Anthony Anselmo, Ruslan I Sadreyev, David M Langenau
Cell transplantation into immunodeficient mice has revolutionized our understanding of regeneration, stem cell self-renewal, and cancer; yet models for direct imaging of engrafted cells has been limited. Here, we characterize zebrafish with mutations in recombination activating gene 2 (rag2), DNA-dependent protein kinase (prkdc), and janus kinase 3 (jak3). Histology, RNA sequencing, and single-cell transcriptional profiling of blood showed that rag2 hypomorphic mutant zebrafish lack T cells, whereas prkdc deficiency results in loss of mature T and B cells and jak3 in T and putative Natural Killer cells...
November 14, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27720937/using-zebrafish-models-of-leukemia-to-streamline-drug-screening-and-discovery
#10
REVIEW
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...
January 2017: Experimental Hematology
https://www.readbyqxmd.com/read/27550848/murine-tribbles-homolog-2-deficiency-affects-erythroid-progenitor-development-and-confers-macrocytic-anemia-on-mice
#11
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
https://www.readbyqxmd.com/read/27486814/nucleophosmin-leukemogenic-mutant-activates-wnt-signaling-during-zebrafish-development
#12
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...
August 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27464808/modeling-leukemogenesis-in-the-zebrafish-using-genetic-and-xenograft-models
#13
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
https://www.readbyqxmd.com/read/27457538/c-myb-hyperactivity-leads-to-myeloid-and-lymphoid-malignancies-in-zebrafish
#14
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...
January 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27195189/the-progress-of-early-growth-response-factor-1-and-leukemia
#15
REVIEW
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
https://www.readbyqxmd.com/read/27165361/zebrafish-models-of-human-leukemia-technological-advances-and-mechanistic-insights
#16
REVIEW
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
https://www.readbyqxmd.com/read/27165353/transcriptomic-analyses-in-zebrafish-cancer-models-for-global-gene-expression-and-pathway-discovery
#17
REVIEW
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
https://www.readbyqxmd.com/read/27139488/single-cell-transcriptional-analysis-of-normal-aberrant-and-malignant-hematopoiesis-in-zebrafish
#18
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
https://www.readbyqxmd.com/read/27118402/creb-engages-c-ebp%C3%AE-to-initiate-leukemogenesis
#19
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
https://www.readbyqxmd.com/read/27112172/in-vivo-chemical-screen-in-zebrafish-embryos-identifies-regulators-of-hematopoiesis-using-a-semiautomated-imaging-assay
#20
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
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