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https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#1
F Zhao, Y Shi, Y Huang, Y Zhan, L Zhou, Y Li, Y Wan, H Li, H Huang, H Ruan, L Luo, L Li
Interferon regulatory factor (IRF)-8 is a critical transcription factor involved in the pathogenesis of myeloid neoplasia. However, the underlying mechanisms in vivo are not well known. Investigation of irf8 mutant zebrafish in this study indicated that Irf8 is evolutionarily conserved as an essential neoplastic suppressor through tight control of the proliferation and longevity of myeloid cells. Surviving irf8 mutants quickly developed a myeloproliferative neoplasm (MPN)-like disease with enhanced output of the myeloid precursors, which recurred after transplantation...
June 19, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28602865/anti-angiogenic-activity-of-water-extract-from-euphorbia-pekinensis-rupr
#2
Wenting Zhang, Bin Liu, Yaru Feng, Jie Liu, Zhiqiang Ma, Jian Zheng, Qing Xia, Yuanyuan Ni, Farong Li, Ruichao Lin
ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia pekinensis Rupr. (EP) is a Euphorbia species of Euphorbiaceae, which is widely used in traditional Chinese medicine. It has been reported to exhibit therapeutic effects on solid tumors, leukemias, and malignant ascites although underlying molecular mechanisms are poorly delineated. Anti-angiogenic therapy is a recognized strategy for treating cancer-based solid tumors, and is also associated with malignant ascites treatment. STUDY AIM: To study the anti-angiogenic properties of the water extract of EP vinegar preparation (WEVEP)...
June 7, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28525947/dianhydrogalactitol-a-potential-multitarget-agent-inhibits-glioblastoma-migration-invasion-and-angiogenesis
#3
Xia Jiang, Yinmei Huang, Xiaojie Wang, Qiaofang Liang, Yingjie Li, Fuji Li, Xuanhao Fu, Chonghuan Huang, Huagang Liu
The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28518092/isolation-of-the-side-population-in-myc-induced-t-cell-acute-lymphoblastic-leukemia-in-zebrafish
#4
Margaret M Pruitt, Wilfredo Marin, Michael R Waarts, Jill L O de Jong
Heterogeneous cell populations, from either healthy or malignant tissues, may contain a population of cells characterized by a differential ability to efflux the DNA-binding dye Hoechst 33342. This "side population" of cells can be identified using flow cytometric methods after the Hoechst 33342 dye is excited by an ultraviolet (UV) laser. The side population of many cell types contains stem- or progenitor-like cells. However, not all cell types have an identifiable side population. Danio rerio, zebrafish, have a robust in vivo model of T-cell acute lymphoblastic leukemia (T-ALL), but whether these zebrafish T-ALLs have a side population is unknown...
May 4, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28369036/chromatin-remodeling-factor-smarcd2-regulates-transcriptional-networks-controlling-differentiation-of-neutrophil-granulocytes
#5
Maximilian Witzel, Daniel Petersheim, Yanxin Fan, Ehsan Bahrami, Tomas Racek, Meino Rohlfs, Jacek Puchałka, Christian Mertes, Julien Gagneur, Christoph Ziegenhain, Wolfgang Enard, Asbjørg Stray-Pedersen, Peter D Arkwright, Miguel R Abboud, Vahid Pazhakh, Graham J Lieschke, Peter M Krawitz, Maik Dahlhoff, Marlon R Schneider, Eckhard Wolf, Hans-Peter Horny, Heinrich Schmidt, Alejandro A Schäffer, Christoph Klein
We identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, we identified three homozygous loss-of-function mutations in SMARCD2...
May 2017: Nature Genetics
https://www.readbyqxmd.com/read/28335858/netting-novel-regulators-of-hematopoiesis-and-hematologic-malignancies-in-zebrafish
#6
REVIEW
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
#7
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
#8
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
#9
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
#10
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...
March 15, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28028313/aberrant-activation-of-the-gimap-enhancer-by-oncogenic-transcription-factors-in-t-cell-acute-lymphoblastic-leukemia
#11
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
#12
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
#13
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 (MPL) protein gene 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 the TALEN (transcription activator-like effector nuclease) technology, we created a zebrafish mpl mutant to model human CAMT. Disruption of zebrafish mpl lead to a severe reduction in thrombocytes and a high bleeding tendency, as well as deficiencies in adult hematopoietic stem/progenitor cells...
November 29, 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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