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https://www.readbyqxmd.com/read/28096094/platelet-cd34-expression-and-%C3%AE-%C3%AE-granule-abnormalities-in-gfi1b-and-runx1-related-familial-bleeding-disorders
#1
Anna E Marneth, Waander L van Heerde, Konnie M Hebeda, Britta A P Laros-van Gorkom, Wideke Barteling, Brigith Willemsen, Aniek O de Graaf, Annet Simons, Joop H Jansen, Frank Preijers, Marjolijn C Jongmans, Bert A van der Reijden
No abstract text is available yet for this article.
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28093006/blood-malignancies-presenting-with-mutations-at-equivalent-residues-in-runx1-2-suggest-a-common-leukemogenic-pathway
#2
Michele Callea, Fabiana Fattori, Enrico Silvio Bertini, Francisco Cammarata-Scalisi, Francesco Callea, Emanuele Bellacchio
No abstract text is available yet for this article.
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28092997/the-t-8-21-fusion-protein-runx1-eto-downregulates-pkm2-in-acute-myeloid-leukemia-cells
#3
Jin-Song Yan, Yi-Dong Li, Su-Hui Liu, Qian-Qian Yin, Xin-Yi Liu, Li Xia, Ying Lu
No abstract text is available yet for this article.
January 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28075530/dysregulation-of-pldn-pallidin-is-a-mechanism-for-platelet-dense-granule-deficiency-in-runx1-haplodeficiency
#4
G F Mao, L E Goldfinger, D C Fan, M P Lambert, G Jalagadugula, R Freishtat, A K Rao
BACKGROUND: Inherited RUNX1 haplodeficiency is associated with thrombocytopenia and platelet dysfunction. Dense granule (DG) deficiency is reported in patients with RUNX1 haplodeficiency, but the molecular mechanisms are unknown. Platelet mRNA expression profiling in a patient previously reported by us with a RUNX1 mutation and platelet dysfunction showed decreased expression of PLDN (BLOC1S6), which encodes for pallidin, a subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) involved in granule biogenesis...
January 11, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28070990/a-targeted-next-generation-sequencing-in-the-molecular-risk-stratification-of-adult-acute-myeloid-leukemia-implications-for-clinical-practice
#5
Po-Han Lin, Huei-Ying Li, Sheng-Chih Fan, Tzu-Hang Yuan, Ming Chen, Yu-Hua Hsu, Yu-Hsuan Yang, Long-Yuan Li, Su-Peng Yeh, Li-Yuan Bai, Yu-Min Liao, Chen-Yuan Lin, Ching-Yun Hsieh, Ching-Chan Lin, Che-Hung Lin, Ming-Yu Lien, Tzu-Ting Chen, Yen-Hsuan Ni, Chang-Fang Chiu
Conventional cytogenetics can categorize patients with acute myeloid leukemia (AML) into favorable, intermediate, and unfavorable-risk groups; however, patients with intermediate-risk cytogenetics represent the major population with variable outcomes. Because molecular profiling can assist with AML prognosis and next-generation sequencing allows simultaneous sequencing of many target genes, we analyzed 260 genes in 112 patients with de novo AML who received standard treatment. Multivariate analysis showed that karyotypes and mutation status of TET2, PHF6, KIT, and NPM1(mutation) /FLT3- internal tandem duplication (ITD)(negative) were independent prognostic factors for the entire cohort...
January 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28063722/concordance-of-two-approaches-in-monitoring-of-minimal-residual-disease-in-b-precursor-acute-lymphoblastic-leukemia-fusion-transcripts-and-leukemia-associated-immunophenotypes
#6
Ying-Jung Huang, Elaine Coustan-Smith, Hsiao-Wen Kao, Hsi-Che Liu, Shih-Hsiang Chen, Chih-Cheng Hsiao, Chao-Ping Yang, Tang-Her Jaing, Ting-Chi Yeh, Ming-Chung Kuo, Chang-Liang Lai, Chia-Hui Chang, Dario Campana, Der-Cherng Liang, Lee-Yung Shih
BACKGROUND: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry...
January 4, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28063378/overexpression-of-ptp4a3-in-etv6-runx1-acute-lymphoblastic-leukemia
#7
Toni Grönroos, Susanna Teppo, Juha Mehtonen, Saara Laukkanen, Thomas Liuksiala, Matti Nykter, Merja Heinäniemi, Olli Lohi
Cell signalling, which is often derailed in cancer, is a network of multiple interconnected pathways with numerous feedback mechanisms. Dynamics of cell signalling is intimately regulated by addition and removal of phosphate groups by kinases and phosphatases. We examined expression of members of the PTP4A family of phosphatases across acute leukemias. While expression of PTP4A1 and PTP4A2 remained relatively unchanged across diseases, PTP4A3 showed marked overexpression in ETV6-RUNX1 and BCR-ABL1 subtypes of precursor B cell acute lymphoblastic leukemia...
December 26, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28063196/asxl2-mutations-are-frequently-found-in-pediatric-aml-patients-with-t-8-21-runx1-runx1t1-and-associated-with-a-better-prognosis
#8
Genki Yamato, Norio Shiba, Kenichi Yoshida, Yuichi Shiraishi, Yusuke Hara, Kentaro Ohki, Jun Okubo, Haruna Okuno, Kenichi Chiba, Hiroko Tanaka, Akitoshi Kinoshita, Hiroshi Moritake, Nobutaka Kiyokawa, Daisuke Tomizawa, Myoung-Ja Park, Manabu Sotomatsu, Takashi Taga, Souichi Adachi, Akio Tawa, Keizo Horibe, Hirokazu Arakawa, Satoru Miyano, Seishi Ogawa, Yasuhide Hayashi
ASXL2 is an epigenetic regulator involved in polycomb repressive complex regulation or recruitment. Clinical features of pediatric AML patients with ASXL2 mutations remain unclear. Thus, we investigated frequencies of ASXL1 and ASXL2 mutations, clinical features of patients with these mutations, correlations of these mutations with other genetic alterations including BCOR/BCORL1 and cohesin complex component genes, and prognostic impact of these mutations in 369 pediatric patients with de novo AML (0-17 years)...
January 7, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28061442/genetic-variants-in-the-tgf%C3%AE-signaling-pathway-influence-expression-of-mirnas-in-colon-and-rectal-normal-mucosa-and-tumor-tissue
#9
Martha L Slattery, Andromahi Trivellas, Andrew J Pellatt, Lila E Mullany, John R Stevens, Roger K Wolff, Jennifer S Herrick
The TGF-β signaling pathway is involved in regulation of cell growth, angiogenesis, and metastasis. We test the hypothesis that genetic variation in the TGF-β signaling pathway alters miRNA expression.We use data from 1188 colorectal cancer cases to evaluate associations between 80 SNPs in 21 genes.Seven variants eIF4E rs12498533, NFκB1 rs230510, TGFB1 rs4803455, TGFBR1 rs1571590 and rs6478974, SMAD3 rs3743343, and RUNX1 rs8134179 were associated with expression level of miRNAs in normal colorectal mucosa...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28055425/igf1-regulates-runx1-expression-via-irs1-2-implications-for-antler-chondrocyte-differentiation
#10
Zhan-Qing Yang, Hong-Liang Zhang, Cui-Cui Duan, Shuang Geng, Kai Wang, Hai-Fan Yu, Zhan-Peng Yue, Bin Guo
Although IGF1 is important for the proliferation and differentiation of chondrocytes, its underlying molecular mechanism is still unknown. Here we addressed the physiological function of IGF1 in antler cartilage and explored the interplay of IGF1, IRS1/2 and RUNX1 in chondrocyte differentiation. The results showed that IGF1 was highly expressed in antler chondrocytes. Exogenous rIGF1 could increase the proliferation of chondrocytes and cell proportion in the S phase, whereas IGF1R inhibitor PQ401 abrogated the induction by rIGF1...
January 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28055379/relationship-between-runx1-and-axin1-in-er-negative-versus-er-positive-breast-cancer
#11
Nyam-Osor Chimge, Sara Ahmed-Alnassar, Baruch Frenkel
RUNX1 plays opposing roles in breast cancer: a tumor suppressor in estrogen receptor-positive (ER(+)) disease and an oncogenic role in ER-negative (ER(-)) tumors. Potentially mediating the former, we have recently reported that RUNX1 prevents estrogen-driven suppression of the mRNA encoding the tumor suppressor AXIN1. Accordingly, AXIN1 protein expression was diminished upon RUNX1 silencing in ER(+) breast cancer cells and was positively correlated with AXIN1 protein expression across tumors with high levels of ER (1) ...
January 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28030795/aml-associated-oncofusion-proteins-pml-rara-aml1-eto-and-cbfb-myh11-target-runx-ets-factor-binding-sites-to-modulate-h3ac-levels-and-drive-leukemogenesis
#12
Abhishek A Singh, Amit Mandoli, Koen H M Prange, Marko Laakso, Joost H A Martens
Chromosomal translocations are one of the hallmarks of acute myeloid leukemia (AML), often leading to gene fusions and expression of an oncofusion protein. Over recent years it has become clear that most of the AML associated oncofusion proteins molecularly adopt distinct mechanisms for inducing leukemogenesis. Still these unique molecular properties of the chimeric proteins converge and give rise to a common pathogenic molecular mechanism. In the present study we compared genome-wide DNA binding and transcriptome data associated with AML1-ETO, CBFB-MYH11 and PML-RARA oncofusion protein expression to identify unique and common features...
December 24, 2016: Oncotarget
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
#13
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
#14
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...
December 28, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28012022/runx1-regulates-migration-invasion-and-angiogenesis-via-p38-mapk-pathway-in-human-glioblastoma
#15
Kant Sangpairoj, Pornpun Vivithanaporn, Somjai Apisawetakan, Sukumal Chongthammakun, Prasert Sobhon, Kulathida Chaithirayanon
Runt-related transcription factor 1 (RUNX1) is essential for the establishment of fetal and adult hematopoiesis and neuronal development. Aberrant expression of RUNX1 led to proliferation and metastasis of several cancers. The aim of the present study was to investigate the role of RUNX1 in migration, invasion, and angiogenesis of human glioblastoma using IL-1β-treated U-87 MG human glioblastoma cells as a model. IL-1β at 10 ng/ml stimulated translocation of RUNX1 into the nucleus with increased expressions of RUNX1, MMP-1, MMP-2, MMP-9, MMP-19, and VEGFA in U-87 MG cells...
December 24, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28007920/role-of-il-32-in-hiv-reactivation-and-its-link-to-hiv-hsv-coinfection
#16
Pedro M M Mesquita, Paula Preston-Hurlburt, Marla J Keller, Nalini Vudattu, Lilia Espinoza, Michelle Altrich, Kathryn Anastos, Kevan C Herold, Betsy C Herold
BACKGROUND: HSV-2 exacerbates HIV by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T cell populations and HIV reservoirs. METHODS: Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative (HIV(+)/HSV-2(+) or HIV(+)/HSV-2(-)) and HIV-uninfected controls were analyzed by flow cytometry. HIV cell-associated (CA)-DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant IL-32γ, and a RUNX1 inhibitor...
December 22, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28004528/minimal-residual-disease-monitoring-in-childhood-b-lymphoblastic-leukemia-with-t-12-21-p13-q22-etv6-runx1-concordant-results-using-quantitation-of-fusion-transcript-and-flow-cytometry
#17
S J Alm, C Engvall, J Asp, L Palmqvist, J Abrahamsson, L Fogelstrand
INTRODUCTION: The translocation t(12;21)(p13;q22) resulting in the fusion gene ETV6-RUNX1, is the most frequent gene fusion in childhood B lymphoblastic leukemia. In the Nordic Society of Paediatric Haematology and Oncology ALL-2008 treatment protocol, treatment stratification in B-lineage ALL is based on results of minimal residual disease (MRD) analysis with fluorescence-activated cell sorting (FACS). In this study, we determined whether RT-qPCR of the ETV6-RUNX1 fusion transcript can be a reliable alternative for MRD analysis...
December 22, 2016: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/27997762/acquired-tet2-mutation-in-one-patient-with-familial-platelet-disorder-with-predisposition-to-aml-led-to-the-development-of-pre-leukaemic-clone-resulting-in-t2-all-and-aml-m0
#18
Vladimir T Manchev, Hind Bouzid, Iléana Antony-Debré, Betty Leite, Guillaume Meurice, Nathalie Droin, Thomas Prebet, Régis T Costello, William Vainchenker, Isabelle Plo, M'boyba Diop, Elizabeth Macintyre, Vahid Asnafi, Rémi Favier, Véronique Baccini, Hana Raslova
Familial platelet disorder with predisposition to acute myeloid leukaemia (FPD/AML) is characterized by germline RUNX1 mutations, thrombocytopaenia, platelet dysfunction and a risk of developing acute myeloid and in rare cases lymphoid T leukaemia. Here, we focus on a case of a man with a familial history of RUNX1(R174Q) mutation who developed at the age of 42 years a T2-ALL and, 2 years after remission, an AML-M0. Both AML-M0 and T2-ALL blast populations demonstrated a loss of 1p36.32-23 and 17q11.2 regions as well as other small deletions, clonal rearrangements of both TCRγ and TCRδ and a presence of 18 variants at a frequency of more than 40%...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27992414/dynamics-of-clonal-evolution-in-myelodysplastic-syndromes
#19
Hideki Makishima, Tetsuichi Yoshizato, Kenichi Yoshida, Mikkael A Sekeres, Tomas Radivoyevitch, Hiromichi Suzuki, Bartlomiej Przychodzen, Yasunobu Nagata, Manja Meggendorfer, Masashi Sanada, Yusuke Okuno, Cassandra Hirsch, Teodora Kuzmanovic, Yusuke Sato, Aiko Sato-Otsubo, Thomas LaFramboise, Naoko Hosono, Yuichi Shiraishi, Kenichi Chiba, Claudia Haferlach, Wolfgang Kern, Hiroko Tanaka, Yusuke Shiozawa, Inés Gómez-Seguí, Holleh D Husseinzadeh, Swapna Thota, Kathryn M Guinta, Brittney Dienes, Tsuyoshi Nakamaki, Shuichi Miyawaki, Yogen Saunthararajah, Shigeru Chiba, Satoru Miyano, Lee-Yung Shih, Torsten Haferlach, Seishi Ogawa, Jaroslaw P Maciejewski
To elucidate differential roles of mutations in myelodysplastic syndromes (MDS), we investigated clonal dynamics using whole-exome and/or targeted sequencing of 699 patients, of whom 122 were analyzed longitudinally. Including the results from previous reports, we assessed a total of 2,250 patients for mutational enrichment patterns. During progression, the number of mutations, their diversity and clone sizes increased, with alterations frequently present in dominant clones with or without their sweeping previous clones...
December 19, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27974636/myeloperoxidase-enhances-etoposide-and-mitoxantrone-mediated-dna-damage-a-target-for-myeloprotection-in-cancer-chemotherapy
#20
Mandeep Atwal, Emma L Lishman, Caroline A Austin, Ian G Cowell
Myeloperoxidase is expressed exclusively in granulocytes and immature myeloid cells and transforms the topoisomerase II (TOP2) poisons etoposide and mitoxantrone to chemical forms that have altered DNA damaging properties. TOP2 poisons are valuable and widely used anticancer drugs, but they are associated with the occurrence of secondary acute myeloid leukemias. These factors have led to the hypothesis that myeloperoxidase inhibition could protect hematopoietic cells from TOP2 poison-mediated genotoxic damage and, therefore, reduce the rate of therapy-related leukemia...
January 2017: Molecular Pharmacology
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