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https://www.readbyqxmd.com/read/29326336/arid5b-as-a-critical-downstream-target-of-the-tal1-complex-that-activates-the-oncogenic-transcriptional-program-and-promotes-t-cell-leukemogenesis
#1
Wei Zhong Leong, Shi Hao Tan, Phuong Cao Thi Ngoc, Stella Amanda, Alice Wei Yee Yam, Wei-Siang Liau, Zhiyuan Gong, Lee N Lawton, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1/SCL induces an aberrant transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL) cells. However, the critical factors that are directly activated by TAL1 and contribute to T-ALL pathogenesis are largely unknown. Here, we identified AT-rich interactive domain 5B (ARID5B) as a collaborating oncogenic factor involved in the transcriptional program in T-ALL. ARID5B expression is down-regulated at the double-negative 2-4 stages in normal thymocytes, while it is induced by the TAL1 complex in human T-ALL cells...
January 11, 2018: Genes & Development
https://www.readbyqxmd.com/read/29249771/synthesis-of-novel-class-of-n-alkyl-isatin-3-iminobenzoic-acid-derivatives-and-their-biological-activity-in-zebrafish-embryos-and-human-cancer-cell-lines
#2
Muhammad Farooq, Zainab M Almarhoon, Nael Abu Taha, Almohannad A R Baabbad, Mohammed A Al-Wadaan, Ayman El-Faham
Isatin (1H-indole-2,3-dione) and many of its derivatives are reported to have pharmacological properties. In this study, we report the synthesis and biological activity of a new class of N-alkyl-isatin-3-iminobenzoic acid derivatives prepared via the condensation of N-alkyl isatin with 4-aminobenzoic acid by conventional, microwave, and ultrasonic methods. Microwave irradiation yielded the products in a shorter reaction time with higher yields and purities. The compounds were screened in zebrafish embryos, and also in three human cancer cell lines (MCF7, HepG2, and Jurkat) and one normal human cell line i...
December 16, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29249175/a-tool-compound-targeting-the-core-binding-factor-runt-domain-to-disrupt-binding-to-cbf%C3%AE-in-leukemic-cells
#3
Zaw Min Oo, Anuradha Illendula, Jolanta Grembecka, Charles Schmidt, Yunpeng Zhou, Virginie Esain, Wanda Kwan, Isaura Frost, Trista E North, Roger A Rajewski, Nancy A Speck, John H Bushweller
The core binding factor (CBF) gene RUNX1 is a target of chromosomal translocations in leukemia, including t(8;21) in acute myeloid leukemia (AML). Normal CBF function is essential for activity of AML1-ETO, product of the t(8;21), and for survival of several leukemias lacking RUNX1 mutations. Using virtual screening and optimization, we developed Runt domain inhibitors which bind to the Runt domain and disrupt its interaction with CBFβ. On-target activity was demonstrated by the Runt domain inhibitors' ability to depress hematopoietic cell formation in zebrafish embryos, reduce growth and induce apoptosis of t(8;21) AML cell lines, and reduce progenitor activity of mouse and human leukemia cells harboring the t(8;21), but not normal bone marrow cells...
December 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29246646/the-dialkyl-resorcinol-stemphol-disrupts-calcium-homeostasis-to-trigger-programmed-immunogenic-necrosis-in-cancer
#4
Seungwon Ji, Jin-Young Lee, Jan Schrör, Aloran Mazumder, Dong Man Jang, Sébastien Chateauvieux, Michael Schnekenburger, Che Ry Hong, Christo Christov, Hyoung Jin Kang, Youngjo Lee, Byung Woo Han, Kyu-Won Kim, Hee-Young Shin, Mario Dicato, Claudia Cerella, Gabriele M König, Barbora Orlikova, Marc Diederich
Stemphol (STP) is a novel druggable phytotoxin triggering mixed apoptotic and non-apoptotic necrotic-like cell death in human acute myeloid leukemia (AML). Use of several chemical inhibitors highlighted that STP-induced non-canonical programmed cell death was Ca2+-dependent but independent of caspases, poly (ADP-ribose) polymerase-1, cathepsin, or calpains. Similar to thapsigargin, STP led to increased cytosolic Ca2+ levels and computational docking confirmed binding of STP within the thapsigargin binding pocket of the sarco/endoplasmic reticulum (ER) Ca2+-ATPase (SERCA)...
December 12, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29168762/dual-roles-of-fer-kinase-are-required-for-proper-hematopoiesis-and-vascular-endothelium-organization-during-zebrafish-development
#5
Emily M Dunn, Elizabeth J Billquist, Amy L VanderStoep, Phillip G Bax, Laura M Westrate, Lisa K McLellan, Shelby C Peterson, Jeffrey P MacKeigan, Aaron P Putzke
Fer kinase, a protein involved in the regulation of cell-cell adhesion and proliferation, has been shown to be required during invertebrate development and has been implicated in leukemia, gastric cancer, and liver cancer. However, in vivo roles for Fer during vertebrate development have remained elusive. In this study, we bridge the gap between the invertebrate and vertebrate realms by showing that Fer kinase is required during zebrafish embryogenesis for normal hematopoiesis and vascular organization with distinct kinase dependent and independent functions...
November 23, 2017: Biology
https://www.readbyqxmd.com/read/28974511/tox-regulates-growth-dna-repair-and-genomic-instability-in-t-cell-acute-lymphoblastic-leukemia
#6
Riadh Lobbardi, Jordan Pinder, Barbara Martinez-Pastor, Marina Theodorou, Jessica S Blackburn, Brian J Abraham, Yuka Namiki, Marc Mansour, Nouran S Abdelfattah, Aleksey Molodtsov, Gabriela Alexe, Debra Toiber, Manon de Waard, Esha Jain, Myriam Boukhali, Mattia Lion, Deepak Bhere, Khalid Shah, Alejandro Gutierrez, Kimberly Stegmaier, Lewis B Silverman, Ruslan I Sadreyev, John M Asara, Marjorie A Oettinger, Wilhelm Haas, A Thomas Look, Richard A Young, Raul Mostoslavsky, Graham Dellaire, David M Langenau
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of thymocytes. Using a transgenic screen in zebrafish, thymocyte selection-associated high mobility group box protein (TOX) was uncovered as a collaborating oncogenic driver that accelerated T-ALL onset by expanding the initiating pool of transformed clones and elevating genomic instability. TOX is highly expressed in a majority of human T-ALL and is required for proliferation and continued xenograft growth in mice. Using a wide array of functional analyses, we uncovered that TOX binds directly to KU70/80 and suppresses recruitment of this complex to DNA breaks to inhibit nonhomologous end joining (NHEJ) repair...
November 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28930163/zebrafish-in-translational-cancer-research-insight-into-leukemia-melanoma-glioma-and-endocrine-tumor-biology
#7
REVIEW
Aurora Irene Idilli, Francesca Precazzini, Maria Caterina Mione, Viviana Anelli
Over the past 15 years, zebrafish have emerged as a powerful tool for studying human cancers. Transgenic techniques have been employed to model different types of tumors, including leukemia, melanoma, glioblastoma and endocrine tumors. These models present histopathological and molecular conservation with their human cancer counterparts and have been fundamental for understanding mechanisms of tumor initiation and progression. Moreover, xenotransplantation of human cancer cells in embryos or adult zebrafish offers the advantage of studying the behavior of human cancer cells in a live organism...
September 20, 2017: Genes
https://www.readbyqxmd.com/read/28841206/overexpression-of-sox4-correlates-with-poor-prognosis-of-acute-myeloid-leukemia-and-is-leukemogenic-in-zebrafish
#8
J-W Lu, M-S Hsieh, H-A Hou, C-Y Chen, H-F Tien, L-I Lin
The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status...
August 25, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28753595/clinico-biological-significance-of-suppressor-of-cytokine-signaling-1-expression-in-acute-myeloid-leukemia
#9
H-A Hou, J-W Lu, T-Y Lin, C-H Tsai, W-C Chou, C-C Lin, Y-Y Kuo, C-Y Liu, M-H Tseng, Y-C Chiang, Y-L Peng, J-L Tang, Z Gong, L-I Lin, H-F Tien
Suppressor of cytokine signaling 1 (SOCS1) protein, which encodes a member of signal transducers and activators of transcription-induced inhibitors, takes part in a negative regulation of cytokine signaling. The mechanism of SOCS1 in tumor carcinogenesis is complex and there have been no studies concerning the clinic-biologic implication of SOCS1 expression in acute myeloid leukemia (AML). Here, we first identified that higher bone marrow (BM) SOCS1 expression was closely associated with older age, FLT3-ITD, NPM1 and DNMT3A mutations, but negatively correlated with CEBPA mutation in patients with de novo AML...
July 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28735489/a-zebrafish-model-for-evaluating-the-function-of-human-leukemic-gene-idh1-and-its-mutation
#10
Alvin C H Ma, Xiangguo Shi, Bai-Liang He, Yuhan Guo, Anskar Y H Leung
The recent advent of next-generation sequencing (NGS) has greatly accelerated identification of gene mutations in myeloid malignancies at unprecedented speed that will soon outpace their functional validation by conventional laboratory techniques and animal models. A high-throughput whole-organism model is useful for the functional validation of new mutations. We recently reported the use of zebrafish to evaluate the hematopoietic function of isocitrate dehydrogenase 1 (IDH1) and the effects of expressing human IDH1-R132H that is frequently identified in human acute myeloid leukemia (AML), in myelopoiesis, with a view to develop zebrafish as a model of AML...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28642593/transforming-growth-factor-%C3%AE-1-regulates-the-nascent-hematopoietic-stem-cell-niche-by-promoting-gluconeogenesis
#11
C-Y Zhang, H-M Yin, H Wang, D Su, Y Xia, L-F Yan, B Fang, W Liu, Y-M Wang, A-H Gu, Y Zhou
The understanding of hematopoietic stem cell (HSC) emergence is important to generate HSCs from pluripotent precursors. However, integrated signaling network that regulates the niche of nascent HSCs remains unclear. Herein, we uncovered a novel role of TGF-β1 in the metabolic niche of HSC emergence using the tgf-β1b(-/-) zebrafish. Our findings first showed that Tgf-β1 transcripts were enriched in the nascent HSCs. Loss of tgf-β1b caused a decrease of nascent HSCs within the aorta-gonad-mesonephros. Moreover, tgf-β1b(+) cells were runx1(+) HSCs and underwent an endothelial-to-hematopoietic-transition process...
June 23, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28626217/irf8-regulates-the-progression-of-myeloproliferative-neoplasm-mpn-like-syndrome-via-mertk-signaling-in-zebrafish
#12
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
#13
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)...
July 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28525947/dianhydrogalactitol-a-potential-multitarget-agent-inhibits-glioblastoma-migration-invasion-and-angiogenesis
#14
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
#15
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
#16
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
#17
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
#18
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
#19
REVIEW
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
#20
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
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