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https://www.readbyqxmd.com/read/27851970/the-hematopoietic-transcription-factors-runx1-and-erg-prevent-aml1-eto-oncogene-overexpression-and-onset-of-the-apoptosis-program-in-t-8-21-amls
#1
Amit Mandoli, Abhishek A Singh, Koen H M Prange, Esther Tijchon, Marjolein Oerlemans, Rene Dirks, Menno Ter Huurne, Albertus T J Wierenga, Eva M Janssen-Megens, Kim Berentsen, Nilofar Sharifi, Bowon Kim, Filomena Matarese, Luan N Nguyen, Nina C Hubner, Nagesha A Rao, Emile van den Akker, Lucia Altucci, Edo Vellenga, Hendrik G Stunnenberg, Joost H A Martens
The t(8;21) acute myeloid leukemia (AML)-associated oncoprotein AML1-ETO disrupts normal hematopoietic differentiation. Here, we have investigated its effects on the transcriptome and epigenome in t(8,21) patient cells. AML1-ETO binding was found at promoter regions of active genes with high levels of histone acetylation but also at distal elements characterized by low acetylation levels and binding of the hematopoietic transcription factors LYL1 and LMO2. In contrast, ERG, FLI1, TAL1, and RUNX1 bind at all AML1-ETO-occupied regulatory regions, including those of the AML1-ETO gene itself, suggesting their involvement in regulating AML1-ETO expression levels...
November 15, 2016: Cell Reports
https://www.readbyqxmd.com/read/27797342/high-throughput-screening-in-niche-based-assay-identifies-compounds-to-target-preleukemic-stem-cells
#2
Bastien Gerby, Diogo F T Veiga, Jana Krosl, Sami Nourreddine, Julianne Ouellette, André Haman, Geneviève Lavoie, Iman Fares, Mathieu Tremblay, Véronique Litalien, Elizabeth Ottoni, Milena Kosic, Dominique Geoffrion, Joël Ryan, Paul S Maddox, Jalila Chagraoui, Anne Marinier, Josée Hébert, Guy Sauvageau, Benjamin H Kwok, Philippe P Roux, Trang Hoang
Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T-ALL requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27795542/genetic-and-epigenetic-aberrations-of-pediatric-leukemia-and-clinical-applications
#3
Junko Takita
Pediatric acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Although fusion genes generated by chromosomal rearrangements are the most frequent genetic alterations in pediatric ALL, fusions are insufficient for the development of this disease, and thus, cannot serve as therapeutic targets for ALL. Recently, integrated genetic analysis using next generation sequencing technology has revealed the genetic landscapes of pediatric ALL. These studies disclosed that in addition to fusion genes, aberrations of cell proliferation pathways and epigenetic regulations are also involved in the pathogenesis of pediatric ALL...
2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27759908/translocation-t-8-14-q24-q11-with-concurrent-pten-alterations-and-deletions-of-stil-tal1-and-cdkn2a-b-in-a-pediatric-case-of-acute-t-lymphoblastic-leukemia-a-genetic-profile-associated-with-adverse-prognosis
#4
Jolanta Skalska-Sadowska, Małgorzata Dawidowska, Bronisława Szarzyńska-Zawadzka, Małgorzata Jarmuż-Szymczak, Joanna Czerwińska-Rybak, Ludomiła Machowska, Katarzyna Derwich
We report a pediatric case of acute T-lymphoblastic leukemia (T-ALL) with NOTCH1(wt) , FBXW7(wt) , STIL/TAL1, and PTEN (exons 2, 3, 4, 5) monoallelic deletions, biallelic CDKN2A/B deletion, and a minor t(8;14)(q24;q11)-positive subclone. Undetectable by a flow cytometric minimal residual disease assay, the t(8;14)(q24;q11) subclone expanded as detected by fluorescence in situ hybridization from 5% at diagnosis to 26% before consolidation and 100% at relapse bearing a monoallelic deletion (exons 2, 3) with a new frameshift mutation of PTEN and the same set of remaining molecular alterations...
October 19, 2016: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/27574108/foxp3-downregulation-in-nsclc-mediates-epithelial-mesenchymal-transition-via-nf-%C3%AE%C2%BAb-signaling
#5
Xi Wang, Ying Liu, Lingling Dai, Qi Liu, Liuqun Jia, Huan Wang, Lin An, Xiaogang Jing, Meng Liu, Pengfei Li, Zhe Cheng
Forkhead box P3 (Foxp3) is a member of forkhead box transcription factor family and it was identified as a tumor suppressor in various solid tumors. This study evaluated the expression of Foxp3 in non-small cell lung cancer (NSCLC) and investigated its role in epithelial‑mesenchymal transition (EMT) of cancer cells. qRT-PCR and western blot analysis were used for examining the expression of Foxp3 in NSCLC tissues and the non-tumor tissues. A tissue microarray was constructed and scored for evaluating the clinical significance of Foxp3 expression in NSCLC tissues...
October 2016: Oncology Reports
https://www.readbyqxmd.com/read/27550837/mir-146b-negatively-regulates-migration-and-delays-progression-of-t-cell-acute-lymphoblastic-leukemia
#6
Nádia C Correia, Rita Fragoso, Tânia Carvalho, Francisco J Enguita, João T Barata
Previous results indicated that miR-146b-5p is downregulated by TAL1, a transcription factor critical for early hematopoiesis that is frequently overexpressed in T-cell acute lymphoblastic leukemia (T-ALL) where it has an oncogenic role. Here, we confirmed that miR-146b-5p expression is lower in TAL1-positive patient samples than in other T-ALL cases. Furthermore, leukemia T-cells display decreased levels of miR-146b-5p as compared to normal T-cells, thymocytes and other hematopoietic progenitors. MiR-146b-5p silencing enhances the in vitro migration and invasion of T-ALL cells, associated with increased levels of filamentous actin and chemokinesis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27466818/prediction-and-validation-of-transcription-factors-modulating-the-expression-of-sestrin3-gene-using-an-integrated-computational-and-experimental-approach
#7
Rajneesh Srivastava, Yang Zhang, Xiwen Xiong, Xiaoning Zhang, Xiaoyan Pan, X Charlie Dong, Suthat Liangpunsakul, Sarath Chandra Janga
SESN3 has been implicated in multiple biological processes including protection against oxidative stress, regulation of glucose and lipid metabolism. However, little is known about the factors and mechanisms controlling its gene expression at the transcriptional level. We performed in silico phylogenetic footprinting analysis of 5 kb upstream regions of a diverse set of human SESN3 orthologs for the identification of high confidence conserved binding motifs (BMo). We further analyzed the predicted BMo by a motif comparison tool to identify the TFs likely to bind these discovered motifs...
2016: PloS One
https://www.readbyqxmd.com/read/27443261/stem-cell-leukemia-how-a-talented-actor-can-go-awry-on-the-hematopoietic-stage
#8
N C Correia, M-L Arcangeli, F Pflumio, J T Barata
TAL1/SCL/TCL5 is a critical transcription factor for hematopoietic stem cell maintenance and regulation of early hematopoiesis. However, aberrant expression of TAL1 in committed T-cell precursors is also directly implicated in the development of T-cell leukemia. Roughly 25 years ago TAL1 was identified in early hematopoietic cells and involved in leukemia. Here, we review the wealth of knowledge gained since then on its physiological roles and mechanisms by which TAL1 ectopic expression contributes to leukemogenesis...
October 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27411634/cloche-is-a-bhlh-pas-transcription-factor-that-drives-haemato-vascular-specification
#9
Sven Reischauer, Oliver A Stone, Alethia Villasenor, Neil Chi, Suk-Won Jin, Marcel Martin, Miler T Lee, Nana Fukuda, Michele Marass, Alec Witty, Ian Fiddes, Taiyi Kuo, Won-Suk Chung, Sherveen Salek, Robert Lerrigo, Jessica Alsiö, Shujun Luo, Dominika Tworus, Sruthy M Augustine, Sophie Mucenieks, Björn Nystedt, Antonio J Giraldez, Gary P Schroth, Olov Andersson, Didier Y R Stainier
Vascular and haematopoietic cells organize into specialized tissues during early embryogenesis to supply essential nutrients to all organs and thus play critical roles in development and disease. At the top of the haemato-vascular specification cascade lies cloche, a gene that when mutated in zebrafish leads to the striking phenotype of loss of most endothelial and haematopoietic cells and a significant increase in cardiomyocyte numbers. Although this mutant has been analysed extensively to investigate mesoderm diversification and differentiation and continues to be broadly used as a unique avascular model, the isolation of the cloche gene has been challenging due to its telomeric location...
July 14, 2016: Nature
https://www.readbyqxmd.com/read/27383781/resolving-early-mesoderm-diversification-through-single-cell-expression-profiling
#10
Antonio Scialdone, Yosuke Tanaka, Wajid Jawaid, Victoria Moignard, Nicola K Wilson, Iain C Macaulay, John C Marioni, Berthold Göttgens
In mammals, specification of the three major germ layers occurs during gastrulation, when cells ingressing through the primitive streak differentiate into the precursor cells of major organ systems. However, the molecular mechanisms underlying this process remain unclear, as numbers of gastrulating cells are very limited. In the mouse embryo at embryonic day 6.5, cells located at the junction between the extra-embryonic region and the epiblast on the posterior side of the embryo undergo an epithelial-to-mesenchymal transition and ingress through the primitive streak...
July 14, 2016: Nature
https://www.readbyqxmd.com/read/27347333/gata2-regulates-gata1-expression-through-lsd1-mediated-histone-modification
#11
Yidi Guo, Xueqi Fu, Bo Huo, Yongsen Wang, Jing Sun, Lingyuan Meng, Tian Hao, Zhizhuang Joe Zhao, Xin Hu
The dynamic and reversed expression of GATA1 and GATA2 are essential for proper erythroid differentiation. Our previous work demonstrates that LSD1, a histone H3K4 demethylase, represses GATA2 expression at late stage of erythroid differentiation. K562 and MEL cells were used and cultured in Roswell Park Memorial Institute-1640 medium (RPMI) and Dulbecco's modified Eagle's medium (DMEM), respectively. Western blot assay was used to examine the GATA1, GATA2, TAL1, HDAC1, HDAC2, CoREST and β-actin protein. The immunoprecipitation assay and GST pull-down assay were employed to detect the precipitated protein complexes and investigate the interaction between the proteins...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27342490/-clinical-characteristics-and-treatment-efficacy-of-children-with-sil-tal1-positive-t-cell-acute-lymphoblastic-leukemia
#12
Xiao Liu, Wei-Jing Li, Xiao-Xi Zhao, Chao Gao, Wei Zhao, Jin Jiang, Rui-Dong Zhang, Jing Xie, Hui-Wen Shi, Bin Wang, Yong-Hong Zhang, Xiao-Li Ma, Xuan Zhou, Min-Yuan Wu, Lei Cui, Zhi-Gang Li
OBJECTIVE: To investigate the clinical features, treatment and prognosis of children with SIL-TAL1 fusion gene positive T-cell acute lymphoblastic leukemia (T-ALL). METHODS: The data of 101 children with T-ALL were collected from April 2005 to November 2012 in Beijing Children's Hospital. The common clinical features, early treatment response, minimal residual disease (MRD), event-free survival (EFS) and relapse-free survival (RFS) were compared between children with SIL-TAL1 positive and negative T-ALL...
June 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/27340788/cxcr4-signaling-negatively-modulates-the-bipotential-state-of-hemogenic-endothelial-cells-derived-from-embryonic-stem-cells-by-attenuating-the-endothelial-potential
#13
Tanzir Ahmed, Kiyomi Tsuji-Tamura, Minetaro Ogawa
Hemogenic endothelial cells (HECs) are considered to be the origin of hematopoietic stem cells (HSCs). HECs have been identified in differentiating mouse embryonic stem cells (ESCs) as VE-cadherin(+) cells with both hematopoietic and endothelial potential in single cells. Although the bipotential state of HECs is a key to cell fate decision toward HSCs, the molecular basis of the regulation of the bipotential state has not been well understood. Here, we report that the CD41(+) fraction of CD45(-) CD31(+) VE-cadherin(+) endothelial cells (ECs) from mouse ESCs encompasses an enriched HEC population...
June 24, 2016: Stem Cells
https://www.readbyqxmd.com/read/27276529/hepatitis-b-virus-surface-protein-induced-hpias1-transcription-requires-tal1-e47-myog-nfi-and-mapk-signal-pathways
#14
Hongyan Wang, Di Wu, Xiaofeng Wang, Guang Chen, Yuanya Zhang, Weiming Yan, Xiaoping Luo, Meifang Han, Qin Ning
The protein inhibitor of activated STAT1 (PIAS1) plays important roles in regulating virusinduced chronic hepatitis, but the interaction between hepatitis B virus (HBV) and hPIAS1 is not clear. Our aim was to verify if HBV encoding proteins enhance the transcription of hPIAS1 and which cis-elements and transcription factors were involved in the mechanism. In order to do, so a series of molecular biological methods, along with functional and histological studies, were performed. We found that the HBV surface protein (HBs) enhanced hPIAS1 transcription through the activities of TAL1, E47, myogenin (MYOG), and NFI, dependent on the activation of p38MAPK and ERK signaling pathways in vitro, which might contribute to the ineffectiveness of treatment in CHB patients...
June 8, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27264182/defining-the-minimal-factors-required-for-erythropoiesis-through-direct-lineage-conversion
#15
Sandra Capellera-Garcia, Julian Pulecio, Kishori Dhulipala, Kavitha Siva, Violeta Rayon-Estrada, Sofie Singbrant, Mikael N E Sommarin, Carl R Walkley, Shamit Soneji, Göran Karlsson, Ángel Raya, Vijay G Sankaran, Johan Flygare
Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced erythroid progenitors/precursors (iEPs). We show that Gata1, Tal1, Lmo2, and c-Myc (GTLM) can rapidly convert murine and human fibroblasts directly to iEPs...
June 14, 2016: Cell Reports
https://www.readbyqxmd.com/read/27191957/trib2-suppresses-tumor-initiation-in-notch-driven-t-all
#16
Sarah J Stein, Ethan A Mack, Kelly S Rome, Kostandin V Pajcini, Takuya Ohtani, Lanwei Xu, Yunlei Li, Jules P P Meijerink, Robert B Faryabi, Warren S Pear
Trib2 is highly expressed in human T cell acute lymphoblastic leukemia (T-ALL) and is a direct transcriptional target of the oncogenic drivers Notch and TAL1. In human TAL1-driven T-ALL cell lines, Trib2 is proposed to function as an important survival factor, but there is limited information about the role of Trib2 in primary T-ALL. In this study, we investigated the role of Trib2 in the initiation and maintenance of Notch-dependent T-ALL. Trib2 had no effect on the growth and survival of murine T-ALL cell lines in vitro when expression was blocked by shRNAs...
2016: PloS One
https://www.readbyqxmd.com/read/27171571/repression-of-primitive-erythroid-program-is-critical-for-the-initiation-of-multi-lineage-hematopoiesis-in-mouse-development
#17
Toshiyuki Yamane, Chie Ito, Aya Washino, Kana Isono, Hidetoshi Yamazaki
Formation of the hematopoietic cells occurs in multiple steps. The first hematopoietic cells observed during ontogeny are primitive erythrocytes, which are produced in the early yolk sac within a limited temporal window. Multi-lineage hematopoiesis, which supplies almost the entire repertoire of blood cell lineages, lags behind primitive erythropoiesis in the tissue. However, molecular mechanisms regulating sequential generation of primitive erythrocytes and multipotent hematopoietic progenitors in the yolk sac are largely unknown...
May 12, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27137657/scl-tal1-in-hematopoiesis-and-cellular-reprogramming
#18
T Hoang, J A Lambert, R Martin
SCL, a transcription factor of the basic helix-loop-helix family, is a master regulator of hematopoiesis. Scl specifies lateral plate mesoderm to a hematopoietic fate and establishes boundaries by inhibiting the cardiac lineage. A combinatorial interaction between Scl and Vegfa/Flk1 sets in motion the first wave of primitive hematopoiesis. Subsequently, definitive hematopoietic stem cells (HSCs) emerge from the embryo proper via an endothelial-to-hematopoietic transition controlled by Runx1, acting with Scl and Gata2...
2016: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27137654/the-hematopoietic-stem-and-progenitor-cell-cistrome-gata-factor-dependent-cis-regulatory-mechanisms
#19
K J Hewitt, K D Johnson, X Gao, S Keles, E H Bresnick
Transcriptional regulators mediate the genesis and function of the hematopoietic system by binding complex ensembles of cis-regulatory elements to establish genetic networks. While thousands to millions of any given cis-element resides in a genome, how transcriptional regulators select these sites and how site attributes dictate functional output is not well understood. An instructive system to address this problem involves the GATA family of transcription factors that control vital developmental and physiological processes and are linked to multiple human pathologies...
2016: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27084257/inhibition-of-human-primary-megakaryocyte-differentiation-by-anagrelide-a-gene-expression-profiling-analysis
#20
Kazuki Sakurai, Tohru Fujiwara, Shin Hasegawa, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Minami Yamada-Fujiwara, Ryo Ichinohasama, Hideo Harigae
Anagrelide is a treatment option for patients with essential thrombocythemia. Although the clinical efficacy of anagrelide has been established, there is limited knowledge of the molecular mechanism underlying its effect. Here, we evaluated the effect of anagrelide on primary megakaryocytic progenitors from cord blood-derived CD34-positive cells. Anagrelide treatment reduced the expression of megakaryocytic markers (CD41 and CD61). Microarray analysis was performed to characterize gene profiles altered by exposure to anagrelide...
August 2016: International Journal of Hematology
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