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https://www.readbyqxmd.com/read/29330113/runt-related-transcription-factor-1-runx1-deficiency-attenuates-inflammation-induced-pro-inflammatory-and-pro-labour-mediators-in-myometrium
#1
Martha Lappas
Identifying new targets that regulate myometrial activation are required to develop effective treatments to stop preterm labor. Inflammation, which can be induced by sterile or infective insults, plays a role in initiating and maintaining uterine contractions. Several high throughput transcription screening studies have identified an upregulation of runt-related transcription factor 1 (RUNX1) mRNA expression in myometrium with labor. The role of RUNX1 in labor, however, is not known. We report increased RUNX1 during late gestation which was further augmented in labor, suggesting that RUNX1 may be involved in the transition of the myometrium from a quiescent into a contractile state in preparation for labor...
January 9, 2018: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29328406/mir-141-inhibits-prostatic-cancer-cell-proliferation-and-migration-and-induces-cell-apoptosis-via-targeting-of-runx1
#2
Song Xu, Jingping Ge, Zhengyu Zhang, Wenquan Zhou
Prostate cancer (PCa) is the most commonly diagnosed male malignancy and the second leading cause of male cancer-related deaths. miR-141 has been demonstrated to be inversely correlated with tumorigenicity. In the present study, we investigated the effect of miR-141 and runt-related transcription factor 1 (RUNX1) on PCa cells. We determined that miR-141 was expressed at a low level and RUNX1 was expressed at a high level in PCa tissues in comparison to that in adjacent normal tissues. Upregulation of miR-141 significantly inhibited cell growth, migration and invasion, and promoted cell apoptosis in PCa cells...
January 11, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29326119/association-of-mutations-with-morphologic-dysplasia-in-de-novo-acute-myeloid-leukemia-without-2016-who-classification-defined-cytogenetic-abnormalities
#3
Olga K Weinberg, Christopher J Gibson, Traci M Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L Ebert, Robert P Hasserjian
Despite improvements in our understanding of the molecular basis of acute myeloid leukemia, the association between genetic mutations with morphologic dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies...
January 11, 2018: Haematologica
https://www.readbyqxmd.com/read/29324888/transcription-factor-runx1-is-pro-neurogenic-in-adult-hippocampal-precursor-cells
#4
Hirokazu Fukui, Annette Rünker, Klaus Fabel, Frank Buchholz, Gerd Kempermann
Transcription factor Runx1 (Runt Related Transcription Factor 1), plays an important role in the differentiation of hematopoetic stem cells, angiogenesis and the development of nociceptive neurons. These known functions have in common that they relate to lineage decisions. We thus asked whether such role might also be found for Runx1 in adult hippocampal neurogenesis as a process, in which such decisions have to be regulated lifelong. Runx1 shows a widespread low expression in the adult mouse brain, not particularly prominent in the hippocampus and the resident neural precursor cells...
2018: PloS One
https://www.readbyqxmd.com/read/29321554/mutations-in-dnmt3a-u2af1-and-ezh2-identify-intermediate-risk-acute-myeloid-leukemia-patients-with-poor-outcome-after-cr1
#5
Caner Saygin, Cassandra Hirsch, Bartlomiej Przychodzen, Mikkael A Sekeres, Betty K Hamilton, Matt Kalaycio, Hetty E Carraway, Aaron T Gerds, Sudipto Mukherjee, Aziz Nazha, Ronald Sobecks, Christopher Goebel, Donna Abounader, Jaroslaw P Maciejewski, Anjali S Advani
Intermediate-risk acute myeloid leukemia (IR-AML) is a clinically heterogeneous disease, for which optimal post-remission therapy is debated. The utility of next-generation sequencing information in decision making for IR-AML has yet to be elucidated. We retrospectively studied 100 IR-AML patients, defined by European Leukemia Net classification, who had mutational information at diagnosis, received intensive chemotherapy and achieved complete remission (CR) at Cleveland Clinic (CC). The Cancer Genome Atlas (TCGA) data were used for validation...
January 10, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29316705/translocation-breakpoints-preferentially-occur-in-euchromatin-and-acrocentric-chromosomes
#6
Cheng-Yu Lin, Ankit Shukla, John P Grady, J Lynn Fink, Eloise Dray, Pascal H G Duijf
Chromosomal translocations drive the development of many hematological and some solid cancers. Several factors have been identified to explain the non-random occurrence of translocation breakpoints in the genome. These include chromatin density, gene density and CCCTC-binding factor (CTCF)/cohesin binding site density. However, such factors are at least partially interdependent. Using 13,844 and 1563 karyotypes from human blood and solid cancers, respectively, our multiple regression analysis only identified chromatin density as the primary statistically significant predictor...
January 8, 2018: Cancers
https://www.readbyqxmd.com/read/29311095/5-of-healthy-newborns-have-an-etv6-runx1-fusion-as-revealed-by-dna-based-gipfel-screening
#7
Daniel Schäfer, Marianne Olsen, David Lähnemann, Martin Stanulla, Robert Slany, Kjeld Schmiegelow, Arndt Borkhardt, Ute Fischer
No abstract text is available yet for this article.
January 8, 2018: Blood
https://www.readbyqxmd.com/read/29306105/distinct-gene-alterations-with-a-high-percentage-of-myeloperoxidase-positive-leukemic-blasts-in-de-novo-acute-myeloid-leukemia
#8
Rena Kamijo, Hidehiro Itonaga, Rika Kihara, Yasunobu Nagata, Tomoko Hata, Norio Asou, Shigeki Ohtake, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Tomoki Naoe, Hitoshi Kiyoi, Yasushi Miyazaki
The myeloperoxidase (MPO)-positivity of blasts in bone marrow smears is an important marker for not only the diagnosis, but also the prognosis of acute myeloid leukemia (AML). To investigate the relationship between genetic alterations and MPO-positivity, we performed targeted sequencing for 51 genes and 10 chimeric gene transcripts in 164 newly diagnosed de novo AML patients; 107 and 57 patients were classified as AML with >50% MPO-positive blasts (MPO-high group) and ≤50% MPO-positive blasts, (MPO-low group), respectively...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29300724/a-novel-prospective-isolation-of-murine-fetal-liver-progenitors-to-study-in-utero-hematopoietic-defects
#9
Julia E Draper, Patrycja Sroczynska, Muhammad Z H Fadlullah, Rahima Patel, Gillian Newton, Wolfgang Breitwieser, Valerie Kouskoff, Georges Lacaud
In recent years, highly detailed characterization of adult bone marrow (BM) myeloid progenitors has been achieved and, as a result, the impact of somatic defects on different hematopoietic lineage fate decisions can be precisely determined. Fetal liver (FL) hematopoietic progenitor cells (HPCs) are poorly characterized in comparison, potentially hindering the study of the impact of genetic alterations on midgestation hematopoiesis. Numerous disorders, for example infant acute leukemias, have in utero origins and their study would therefore benefit from the ability to isolate highly purified progenitor subsets...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29299133/domain-retention-in-transcription-factor-fusion-genes-and-its-biological-and-clinical-implications-a-pan-cancer-study
#10
Pora Kim, Leomar Y Ballester, Zhongming Zhao
Genomic rearrangements involving transcription factors (TFs) can form fusion proteins resulting in either enhanced, weakened, or even loss of TF activity. Functional domain (FD) retention is a critical factor in the activity of transcription factor fusion genes (TFFGs). A systematic investigation of FD retention in TFFGs and their outcome (e.g. expression changes) in a pan-cancer study has not yet been completed. Here, we examined the FD retention status in 386 TFFGs across 13 major cancer types and identified 83 TFFGs involving 67 TFs that retained FDs...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296959/somatic-mutations-in-children-with-gata2-associated-myelodysplastic-syndrome-who-lack-other-features-of-gata2-deficiency
#11
Kevin E Fisher, Amy P Hsu, Christopher L Williams, Hadi Sayeed, Brian Y Merritt, M Tarek Elghetany, Steven M Holland, Alison A Bertuch, Maria Monica Gramatges
Approximately 10% of children with primary myelodysplastic syndrome (MDS) have germ line GATA2 mutations, leading to the proposal that all children with primary MDS and certain cytogenetic findings, including monosomy 7, be tested for germ line GATA2 mutations regardless of family history or other clinical features associated with GATA2 deficiency. In adults with familial GATA2-MDS, those with somatic mutations in ASXL1 experience rapid disease progression to acute myeloid leukemia (AML) and poor prognosis after stem cell transplantation; however, the prevalence of somatic mutations in primary pediatric GATA2-MDS is unclear...
February 28, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296817/runx1-regulates-site-specificity-of-dna-demethylation-by-recruitment-of-dna-demethylation-machineries-in-hematopoietic-cells
#12
Takahiro Suzuki, Yuri Shimizu, Erina Furuhata, Shiori Maeda, Mami Kishima, Hajime Nishimura, Saaya Enomoto, Yoshihide Hayashizaki, Harukazu Suzuki
RUNX1 is an essential master transcription factor in hematopoietic development and plays important roles in immune functions. Although the gene regulatory mechanism of RUNX1 has been characterized extensively, the epigenetic role of RUNX1 remains unclear. Here, we demonstrate that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. Overexpression analysis of RUNX1 showed the RUNX1-binding site-directed DNA demethylation. The RUNX1-mediated DNA demethylation was also observed in DNA replication-arrested cells, suggesting an involvement of active demethylation mechanism...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296792/a-4-lncrna-scoring-system-for-prognostication-of-adult-myelodysplastic-syndromes
#13
Chi-Yuan Yao, Ching-Hsuan Chen, Huai-Hsuan Huang, Hsin-An Hou, Chien-Chin Lin, Mei-Hsuan Tseng, Chein-Jun Kao, Tzu-Pin Lu, Wen-Chien Chou, Hwei-Fang Tien
Long noncoding RNAs (lncRNAs) not only participate in normal hematopoiesis but also contribute to the pathogenesis of acute leukemia. However, their clinical and prognostic relevance in myelodysplastic syndromes (MDSs) remains unclear to date. In this study, we profiled lncRNA expressions in 176 adult patients with primary MDS, and identified 4 lncRNAs whose expression levels were significantly associated with overall survival (OS). We then constructed a risk-scoring system with the weighted sum of these 4 lncRNAs...
August 22, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296785/paradoxical-enhancement-of-leukemogenesis-in-acute-myeloid-leukemia-with-moderately-attenuated-runx1-expressions
#14
Ken Morita, Shintaro Maeda, Kensho Suzuki, Hiroki Kiyose, Junichi Taniguchi, Pu Paul Liu, Hiroshi Sugiyama, Souichi Adachi, Yasuhiko Kamikubo
Besides being a classical tumor suppressor, runt-related transcription factor 1 (RUNX1) is now widely recognized for its oncogenic role in the development of acute myeloid leukemia (AML). Here we report that this bidirectional function of RUNX1 possibly arises from the total level of RUNX family expressions. Indeed, analysis of clinical data revealed that intermediate-level gene expression of RUNX1 marked the poorest-prognostic cohort in relation to AML patients with high- or low-level RUNX1 expressions. Through a series of RUNX1 knockdown experiments with various RUNX1 attenuation potentials, we found that moderate attenuation of RUNX1 contributed to the enhanced propagation of AML cells through accelerated cell-cycle progression, whereas profound RUNX1 depletion led to cell-cycle arrest and apoptosis...
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296779/overexpression-of-runx1-short-isoform-has-an-important-role-in-the-development-of-myelodysplastic-myeloproliferative-neoplasms
#15
Hiroko Sakurai, Yuka Harada, Yosuke Ogata, Yuki Kagiyama, Naoki Shingai, Noriko Doki, Kazuteru Ohashi, Toshio Kitamura, Norio Komatsu, Hironori Harada
RUNX1a, but not RUNX1b, is overexpressed in CD34+ cells from patients with myelodysplastic/myeloproliferative neoplasms.SRSF2P95H mutation induces RUNX1a overexpression and a monocytic phenotype in TF-1 cells.
August 8, 2017: Blood Advances
https://www.readbyqxmd.com/read/29296763/a-case-of-lenalidomide-dependent-myelodysplastic-syndrome
#16
Ira J Miller, Wei-Tong Hsu, James Weisberger, Parameswaran Venugopal
A man with cytopenias, dysplasia, excess blasts, P53 and RUNX1 mutations, and ring chromosome 7 recovered after stopping lenalidomide.
July 11, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290625/regulation-of-mammary-luminal-cell-fate-and-tumorigenesis-by-p38%C3%AE
#17
Ivan Del Barco Barrantes, Camille Stephan-Otto Attolini, Konstantin Slobodnyuk, Ana Igea, Sara Gregorio, Sylwia Gawrzak, Roger R Gomis, Angel R Nebreda
Mammary stem and progenitor cells are essential for mammary gland homeostasis and are also candidates for cells of origin of mammary tumors. Here, we have investigated the function of the protein kinase p38α in the mammary gland using mice that delete this protein in the luminal epithelial cells. We show that p38α regulates the fate of luminal progenitor cells through modulation of the transcription factor RUNX1, an important controller of the estrogen receptor-positive cell lineage. We also provide evidence that the regulation of RUNX1 by p38α probably involves the kinase MSK1, which phosphorylates histone H3 at the RUNX1 promoter...
December 21, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/29290585/a-human-ips-model-implicates-embryonic-b-myeloid-fate-restriction-as-developmental-susceptibility-to-b%C3%A2-acute-lymphoblastic-leukemia-associated-etv6-runx1
#18
Charlotta Böiers, Simon E Richardson, Emma Laycock, Alya Zriwil, Virginia A Turati, John Brown, Jason P Wray, Dapeng Wang, Chela James, Javier Herrero, Ewa Sitnicka, Stefan Karlsson, Andrew J H Smith, Sten Erik W Jacobsen, Tariq Enver
ETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19-IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny...
December 27, 2017: Developmental Cell
https://www.readbyqxmd.com/read/29286619/comparison-of-diagnostic-yield-of-a-fish-panel-against-conventional-cytogenetic-studies-for-hematological-malignancies-a-south-indian-referral-laboratory-analysis-of-201-cases
#19
Vishal Ashok, Ramya Ranganathan, Smitha Chander, Sharat Damodar, Sunil Bhat, Nataraj K S, Satish Kumar A, Sachin Suresh Jadav, Mahesh Rajashekaraiah, Sundareshan T S
Objectives: Genetic markers are crucial fort diagnostic and prognostic investigation of hematological malignancies (HM). The conventional cytogenetic study (CCS) has been the gold standard for more than five decades. However, FISH (Fluorescence in Situ Hybridization) testing has become a popular modality owing to its targeted approach and the ability to detect abnormalities in non-mitotic cells. We here aimed to compare the diagnostic yields of a FISH panel against CCS in HMs. Methods: Samples of bone marrow and peripheral blood for a total of 201 HMs were tested for specific gene rearrangements using multi-target FISH and the results were compared with those from CCS...
December 29, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29284783/cd150-and-cd180-are-involved-in-regulation-of-transcription-factors-expression-in-chronic-lymphocytic-leukemia-cells
#20
I Gordiienko, L Shlapatska, V M Kholodniuk, L Kovalevska, T S Ivanivskaya, S P Sidorenko
BACKGROUND: Sequential stages of B-cell development is stringently coordinated by transcription factors (TFs) network that include B-lineage commitment TFs (Ikaros, Runx1/Cbfb, E2A, and FOXO1), B-lineage maintenance TFs (EBF1 and PAX5) and stage specific set of TFs (IRF4, IRF8, BCL6, BLIMP1). Deregulation of TFs expression and activity is often occurs in malignant B cells. The aim of this study was to evaluate TFs expression in chronic lymphocytic leukemia cells taking into consideration CD150 cell surface expression...
December 2017: Experimental Oncology
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