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https://www.readbyqxmd.com/read/28606225/-clinical-characteristics-and-prognostic-analysis-of-children-and-adolescents-over-10-years-of-age-with-acute-lymphoblastic-leukemia
#1
Jun Wu, Ai-Dong Lu, Le-Ping Zhang
OBJECTIVE: To explore the clinical characteristics and prognosis of children and adolescents over 10 years of age with acute lymphoblastic leukemia (ALL). METHODS: A total of 86 newly diagnosed ALL children and adolescents over 10 years of age (62 cases of B-ALL and 24 cases of T-ALL) were enrolled. Clinical characteristics, therapeutic effect and prognostic factors were retrospectively analyzed. Event-free survival (EFS) and overall survival (OS) rates were estimated by the Kaplan-Meier method...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#2
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28545085/splicing-factor-sf3b1k700e-mutant-dysregulates-erythroid-differentiation-via-aberrant-alternative-splicing-of-transcription-factor-tal1
#3
Shuiling Jin, Hairui Su, Ngoc-Tung Tran, Jing Song, Sydney S Lu, Ying Li, Suming Huang, Omar Abdel-Wahab, Yanyan Liu, Xinyang Zhao
More than 60% of myeloid dysplasia syndrome (MDS) contains mutations in genes encoding for splicing factors such as SF3B1, U2AF, SRSF2 and ZRSR2. Mutations in SF3B1 are associated with 80% cases of refractory anemia with ring sideroblast (RARS), a subtype of MDS. SF3B1K700E is the most frequently mutated site among mutations on SF3B1. Yet the molecular mechanisms on how mutations of splicing factors lead to defective erythropoiesis are not clear. SF3B1K700E mutant binds to an RNA binding protein, RBM15, stronger than the wild type SF3B1 protein in co-immunoprecipitation assays...
2017: PloS One
https://www.readbyqxmd.com/read/28520978/ldb1-mediated-enhancer-looping-can-be-established-independent-of-mediator-and-cohesin
#4
Ivan Krivega, Ann Dean
Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected...
May 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28500845/hematopoietic-transcription-factors-and-differential-cofactor-binding-regulate-prkacb-isoform-expression
#5
Olga N Kuvardina, Stefanie Herkt, Annekarin Meyer, Lucas Schneider, Jasmin Yillah, Nicole Kohrs, Halvard Bonig, Erhard Seifried, Carsten Müller-Tidow, Jörn Lausen
Hematopoietic differentiation is controlled by key transcription factors, which regulate stem cell functions and differentiation. TAL1 is a central transcription factor for hematopoietic stem cell development in the embryo and for gene regulation during erythroid/megakaryocytic differentiation. Knowledge of the target genes controlled by a given transcription factor is important to understand its contribution to normal development and disease. To uncover direct target genes of TAL1 we used high affinity streptavidin/biotin-based chromatin precipitation (Strep-CP) followed by Strep-CP on ChIP analysis using ChIP promoter arrays...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28410882/epo-reprograms-the-epigenome-of-erythroid-cells
#6
Andrea A Perreault, Mary Lauren Benton, Mark J Koury, Stephen J Brandt, Bryan J Venters
The hormone erythropoietin (Epo) is required for erythropoiesis, yet its molecular mechanism of action remains poorly understood, particularly with respect to chromatin dynamics. To investigate how Epo modulates the erythroid epigenome, we performed epigenetic profiling using an ex vivo murine cell system that undergoes synchronous erythroid maturation in response to Epo stimulation. Our findings define the repertoire of Epo-modulated enhancers, illuminating a new facet of Epo signaling. First, a large number of enhancers rapidly responded to Epo stimulation, revealing a cis-regulatory network of Epo-responsive enhancers...
July 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28352301/functional-overexpression-of-genes-involved-in-erythritol-synthesis-in-the-yeast-yarrowia-lipolytica
#7
Aleksandra M Mirończuk, Anna Biegalska, Adam Dobrowolski
BACKGROUND: Erythritol, a four-carbon polyol synthesized by microorganisms as an osmoprotectant, is a natural sweetener produced on an industrial scale for decades. Despite the fact that the yeast Yarrowia lipolytica has been reported since the 1970s as an erythritol producer, the metabolic pathway of this polyol has never been characterized. It was shown that erythritol synthesis in yeast occurs via the pentose phosphate pathway (PPP). The oleaginous yeast Y. lipolytica is a good host for converting inexpensive glycerol into a value-added product such as erythritol...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28299656/roles-of-the-runx1-enhancer-in-normal-hematopoiesis-and-leukemogenesis
#8
Wei-Siang Liau, Phuong Cao Thi Ngoc, Takaomi Sanda
Enhancers are regulatory elements in genomic DNA that contain specific sequence motifs that are bound by DNA-binding transcription factors. The activity of enhancers is tightly regulated in an integrated and combinatorial manner, thus yielding complex patterns of transcription in different tissues. Identifying enhancers is crucial to understanding the physiological and pathogenic roles of their target genes. The RUNX1 intronic enhancer, eR1, acts in cis to regulate RUNX1 gene expression in hematopoietic stem cells (HSCs) and hemogenic endothelial cells...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28244490/the-rna-binding-protein-qki5-regulates-primary-mir-124-1-processing-via-a-distal-rna-motif-during-erythropoiesis
#9
Fang Wang, Wei Song, Hongmei Zhao, Yanni Ma, Yuxia Li, Di Zhai, Jingnan Pi, Yanmin Si, Jiayue Xu, Lei Dong, Rui Su, Mengmeng Zhang, Yong Zhu, Xiaoxia Ren, Fei Miao, Wenjie Liu, Feng Li, Junwu Zhang, Aibin He, Ge Shan, Jingyi Hui, Linfang Wang, Jia Yu
MicroRNA (miRNA) biogenesis is finely controlled by complex layers of post-transcriptional regulators, including RNA-binding proteins (RBPs). Here, we show that an RBP, QKI5, activates the processing of primary miR-124-1 (pri-124-1) during erythropoiesis. QKI5 recognizes a distal QKI response element and recruits Microprocessor through interaction with DGCR8. Furthermore, the recruited Microprocessor is brought to pri-124-1 stem loops by a spatial RNA-RNA interaction between two complementary sequences. Thus, mutations disrupting their base-pairing affect the strength of QKI5 activation...
March 2017: Cell Research
https://www.readbyqxmd.com/read/28216155/forced-fog1-expression-in-erythroleukemia-cells-induction-of-erythroid-genes-and-repression-of-myelo-lymphoid-transcription-factor-pu-1
#10
Tohru Fujiwara, Katsuyuki Sasaki, Kei Saito, Shunsuke Hatta, Satoshi Ichikawa, Masahiro Kobayashi, Yoko Okitsu, Noriko Fukuhara, Yasushi Onishi, Hideo Harigae
The transcription factor GATA-1-interacting protein Friend of GATA-1 (FOG1) is essential for proper transcriptional activation and repression of GATA-1 target genes; yet, the mechanisms by which FOG1 exerts its activating and repressing functions remain unknown. Forced FOG1 expression in human K562 erythroleukemia cells induced the expression of erythroid genes (SLC4A1, globins) but repressed that of GATA-2 and PU.1. A quantitative chromatin immunoprecipitation (ChIP) analysis demonstrated increased GATA-1 chromatin occupancy at both FOG1-activated as well as FOG1-repressed gene loci...
April 1, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28181081/genetic-improvement-of-xylose-metabolism-by-enhancing-the-expression-of-pentose-phosphate-pathway-genes-in-saccharomyces-cerevisiae-ir-2-for-high-temperature-ethanol-production
#11
Yosuke Kobayashi, Takehiko Sahara, Toshihiro Suzuki, Saori Kamachi, Akinori Matsushika, Tamotsu Hoshino, Satoru Ohgiya, Yoichi Kamagata, Kazuhiro E Fujimori
The pentose phosphate pathway (PPP) plays an important role in the efficiency of xylose fermentation during cellulosic ethanol production. In simultaneous saccharification and co-fermentation (SSCF), the optimal temperature for cellulase hydrolysis of lignocellulose is much higher than that of fermentation. Successful use of SSCF requires optimization of the expression of PPP genes at elevated temperatures. This study examined the combinatorial expression of PPP genes at high temperature. The results revealed that over-expression of TAL1 and TKL1 in Saccharomyces cerevisiae (S...
February 8, 2017: Journal of Industrial Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28179281/scl-tal1-a-multifaceted-regulator-from-blood-development-to-disease
#12
REVIEW
Catherine Porcher, Hedia Chagraoui, Maiken S Kristiansen
SCL/TAL1 (stem cell leukemia/T-cell acute lymphoblastic leukemia [T-ALL] 1) is an essential transcription factor in normal and malignant hematopoiesis. It is required for specification of the blood program during development, adult hematopoietic stem cell survival and quiescence, and terminal maturation of select blood lineages. Following ectopic expression, SCL contributes to oncogenesis in T-ALL. Remarkably, SCL's activities are all mediated through nucleation of a core quaternary protein complex (SCL:E-protein:LMO1/2 [LIM domain only 1 or 2]:LDB1 [LIM domain-binding protein 1]) and dynamic recruitment of conserved combinatorial associations of additional regulators in a lineage- and stage-specific context...
April 13, 2017: Blood
https://www.readbyqxmd.com/read/28178989/individualized-analysis-reveals-cpg-sites-with-methylation-aberrations-in-almost-all-lung-adenocarcinoma-tissues
#13
Haidan Yan, Qingzhou Guan, Jun He, Yunqing Lin, Juan Zhang, Hongdong Li, Huaping Liu, Yunyan Gu, Zheng Guo, Fei He
BACKGROUND: Due to the heterogeneity of cancer, identifying differentially methylated (DM) CpG sites between a set of cancer samples and a set of normal samples cannot tell us which patients have methylation aberrations in a particular DM CpG site. METHODS: We firstly showed that the relative methylation-level orderings (RMOs) of CpG sites within individual normal lung tissues are highly stable but widely disrupted in lung adenocarcinoma tissues. This finding provides the basis of using the RankComp algorithm, previously developed for differential gene expression analysis at the individual level, to identify DM CpG sites in each cancer tissue compared with its own normal state...
February 8, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28123038/intron-1-gata-site-enhances-alas2-expression-indispensably-during-erythroid-differentiation
#14
Yingchi Zhang, Jingliao Zhang, Wenbin An, Yang Wan, Shihui Ma, Jie Yin, Xichuan Li, Jie Gao, Weiping Yuan, Ye Guo, James Douglas Engel, Lihong Shi, Tao Cheng, Xiaofan Zhu
The first intronic mutations in the intron 1 GATA site (int-1-GATA) of 5-aminolevulinate synthase 2 (ALAS2) have been identified in X-linked sideroblastic anemia (XLSA) pedigrees, strongly suggesting it could be causal mutations of XLSA. However, the function of this int-1-GATA site during in vivo development remains largely unknown. Here, we generated mice lacking a 13 bp fragment, including this int-1-GATA site (T AGATAA: AGCCCC) and found that hemizygous deletion led to an embryonic lethal phenotype due to severe anemia resulting from a lack of ALAS2 expression, indicating that this non-coding sequence is indispensable for ALAS2 expression in vivo Further analyses revealed that this int-1-GATA site anchored the GATA site in intron 8 (int-8-GATA) and the proximal promoter, forming a long-range loop to enhance ALAS2 expression by an enhancer complex including GATA1, TAL1, LMO2, LDB1 and Pol II at least, in erythroid cells...
January 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28065741/essential-roles-for-cdx-in-murine-primitive-hematopoiesis
#15
Travis Brooke-Bisschop, Joanne G A Savory, Tanya Foley, Randy Ringuette, David Lohnes
The Cdx transcription factors play essential roles in primitive hematopoiesis in the zebrafish where they exert their effects, in part, through regulation of hox genes. Defects in hematopoiesis have also been reported in Cdx mutant murine embryonic stem cell models, however, to date no mouse model reflecting the zebrafish Cdx mutant hematopoietic phenotype has been described. This is likely due, in part, to functional redundancy among Cdx members and the early lethality of Cdx2 null mutants. To circumvent these limitations, we used Cre-mediated conditional deletion to assess the impact of concomitant loss of Cdx1 and Cdx2 on murine primitive hematopoiesis...
February 15, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28028966/glycogen-synthase-kinase-3%C3%AE-gsk-3%C3%AE-and-nuclear-factor-kappa-b-nfkb-in-childhood-acute-lymphoblastic-leukemia
#16
Cristian Fabian Layton Tovar, Hugo Mendieta Zerón, Maria Del Socorro Camarillo Romero, Yanko V Fabila Sánchez, Isidoro Tejocote Romero
BACKGROUND: Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in early childhood. In children with acute lymphoblastic leukemia (ALL), the activity of glycogen synthase kinase (GSK-3β) has been associated with changes in the transcriptional activity and expression of nuclear factor kappa beta (NFKB) in the mononuclear cells of bone marrow. OBJECTIVES: The aim of the study was to determine the possible role of glycogen synthase kinase 3beta (GSK-3β) and nuclear factor kappa beta (NFKB) as prognostic variables in pediatric patients with ALL...
November 2016: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/28028313/aberrant-activation-of-the-gimap-enhancer-by-oncogenic-transcription-factors-in-t-cell-acute-lymphoblastic-leukemia
#17
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/27851970/the-hematopoietic-transcription-factors-runx1-and-erg-prevent-aml1-eto-oncogene-overexpression-and-onset-of-the-apoptosis-program-in-t-8-21-amls
#18
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
#19
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
#20
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
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