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https://www.readbyqxmd.com/read/28920929/structural-investigation-of-nucleophosmin-interaction-with-the-tumor-suppressor-fbw7%C3%AE
#1
A Di Matteo, M Franceschini, A Paiardini, A Grottesi, S Chiarella, S Rocchio, C Di Natale, D Marasco, L Vitagliano, C Travaglini-Allocatelli, L Federici
Nucleophosmin (NPM1) is a multifunctional nucleolar protein implicated in ribogenesis, centrosome duplication, cell cycle control, regulation of DNA repair and apoptotic response to stress stimuli. The majority of these functions are played through the interactions with a variety of protein partners. NPM1 is frequently overexpressed in solid tumors of different histological origin. Furthermore NPM1 is the most frequently mutated protein in acute myeloid leukemia (AML) patients. Mutations map to the C-terminal domain and lead to the aberrant and stable localization of the protein in the cytoplasm of leukemic blasts...
September 18, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28918518/micro-rna-profiling-of-exosomes-from-marrow-derived-mesenchymal-stromal-cells-in-patients-with-acute-myeloid-leukemia-implications-in-leukemogenesis
#2
Juliana Barrera-Ramirez, Jessie R Lavoie, Harinad B Maganti, William L Stanford, Caryn Ito, Mitchell Sabloff, Marjorie Brand, Michael Rosu-Myles, Yevgeniya Le, David S Allan
Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified. Of the five candidate miRs identified by differential packaging in exosomes, only miR-26a-5p and miR-101-3p were significantly increased in AML-derived samples while miR-23b-5p, miR-339-3p and miR-425-5p were significantly decreased...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28911263/potential-role-of-oct4-in-leukemogenesis
#3
Tiphanie Picot, Sanae Kesr, Yuenv Wu, Carmen Aanei, Pascale Flandrin-Gresta, Sylvie Tondeur, Emmanuelle Tavernier, Eric Wattel, Denis Guyotat, Lydia Campos
Embryonic stem cells typically show properties of long term self-renewal and lack of differentiation. When appropriately stimulated, they are able to differentiate into all cell lineages, and lose their self-renewal characteristics. These properties are controlled by a series of genes encoding several transcription factors including OCT4, the product of POU5F1 gene. OCT4 is expressed in germ-cell tumors, but also aberrantly in cancers developing in differentiated tissues. In a previous study, we observed a high expression of OCT4 in acute myeloid cell lines and primary cells, regardless of the Acute Myeloid Leukemia subtype...
September 14, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28910419/il-10-mediated-signals-act-as-a-switch-for-lymphoproliferation-in-human-t-cell-leukemia-virus-type-1-infection-by-activating-the-stat3-and-irf4-pathways
#4
Leila Sawada, Yoshiko Nagano, Atsuhiko Hasegawa, Hikari Kanai, Kai Nogami, Sayaka Ito, Tomoo Sato, Yoshihisa Yamano, Yuetsu Tanaka, Takao Masuda, Mari Kannagi
Human T-cell leukemia virus type-1 (HTLV-1) causes two distinct diseases, adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since there are no disease-specific differences among HTLV-1 strains, the etiological mechanisms separating these respective lymphoproliferative and inflammatory diseases are not well understood. In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28895127/evaluation-of-ccaat-enhancer-binding-protein-c-ebp-alpha-cebpa-and-runt-related-transcription-factor-1-runx1-expression-in-patients-with-de-novo-acute-myeloid-leukemia
#5
Fatemeh Salarpour, Kourosh Goudarzipour, Mohammad Hossein Mohammadi, Ahmad Ahmadzadeh, Sara Faraahi, Mehdi Allahbakhshian Farsani
The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR...
September 11, 2017: Annals of Human Genetics
https://www.readbyqxmd.com/read/28892045/mn1-overexpression-is-driven-by-loss-of-dnmt3b-methylation-activity-in-inv-16-pediatric-aml
#6
N S D Larmonie, T C J M Arentsen-Peters, A Obulkasim, D Valerio, E Sonneveld, A A Danen-van Oorschot, V de Haas, D Reinhardt, M Zimmermann, J Trka, A Baruchel, R Pieters, M M van den Heuvel-Eibrink, C M Zwaan, M Fornerod
In acute myeloid leukemia (AML), specific genomic aberrations induce aberrant methylation, thus directly influencing the transcriptional programing of leukemic cells. Therefore, therapies targeting epigenetic processes are advocated as a promising therapeutic tool for AML treatment. However, to develop new therapies, a comprehensive understanding of the mechanism(s) driving the epigenetic changes as a result of acquired genetic abnormalities is necessary. This understanding is still lacking. In this study, we performed genome-wide CpG-island methylation profiling on pediatric AML samples...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28887355/altered-vasculature-in-bone-marrow-drives-leukemogenesis
#7
(no author information available yet)
Nitric oxide promotes vascular permeability and hypoxia in the bone marrow to drive AML.
September 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28887175/epigenetics-in-pediatric-acute-lymphoblastic-leukemia
#8
REVIEW
Jessica Nordlund, Ann-Christine Syvänen
Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. ALL arises from the malignant transformation of progenitor B- and T-cells in the bone marrow into leukemic cells, but the mechanisms underlying this transformation are not well understood. Recent technical advances and decreasing costs of methods for high-throughput DNA sequencing and SNP genotyping have stimulated systematic studies of the epigenetic changes in leukemic cells from pediatric ALL patients. The results emerging from these studies are increasing our understanding of the epigenetic component of leukemogenesis and have demonstrated the potential of DNA methylation as a biomarker for lineage and subtype classification, prognostication, and disease progression in ALL...
September 5, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28883285/genetic-abnormalities-in-core-binding-factor-acute-myeloid-leukemia
#9
Yuichi Ishikawa
Acute myeloid leukemia (AML) is a genetically heterogeneous disease, and its prognosis is stratified on the basis of chromosomal and genetic alterations. Core binding factor (CBF) leukemia consists of AML with t (8;21) (p22;q22) and inv16 (q16q16) /t (16;16) (q16;q16) and is included in AML with recurrent genetic abnormality according to WHO classification. Although CBF-AML is categorized as favorable-risk AML, approximately 40% of patients show relapse. The t (8;21) and inv16 (q16q16) /t (16;16) (q16;q16) result in RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes, respectively; however, the fusion proteins encoded by these genes alone are insufficient for the development of leukemia...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28882949/phe354leu-polymorphism-of-lkb1-is-a-potential-prognostic-factor-for-cytogenetically-normal-acute-myeloid-leukemia
#10
Ming-Yu Yang, Hui-Hua Hsiao, Yi-Chang Liu, Cheng-Ming Hsu, Sheng-Fung Lin, Pai-Mei Lin
BACKGROUND/AIM: Liver kinase B1 (LKB1) is a major activator of the AMP-dependent kinase/mammalian target of rapamycin pathway. The prevalence and the specificity of LKB1 gene mutation in acute myeloid leukemia (AML) have not been well established. This study aimed to examine mutation of LKB1 in AML and its clinical and pathological implications. PATIENTS AND METHODS: Eighty-five patients newly diagnosed with cytogenetically normal AML were analyzed using polymerase chain reaction followed by direct sequencing...
September 2017: In Vivo
https://www.readbyqxmd.com/read/28867167/pediatric-acute-megakaryoblastic-leukemia-multitasking-fusion-proteins-and-oncogenic-cooperations
#11
REVIEW
Cécile K Lopez, Sébastien Malinge, Muriel Gaudry, Olivier A Bernard, Thomas Mercher
Pediatric leukemia presents specific clinical and genetic features from adult leukemia but the underpinning mechanisms of transformation are still unclear. Acute megakaryoblastic leukemia (AMKL) is the malignant accumulation of progenitors of the megakaryocyte lineage that normally produce blood platelets. AMKL is diagnosed de novo, in patients showing a poor prognosis, or in Down syndrome (DS) patients with a better prognosis. Recent data show that de novo AMKL is primarily associated with chromosomal alterations leading to the expression of fusions between transcriptional regulators...
September 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28864482/ascorbate-depletion-reduces-tet2-activity-to-accelerate-leukemogenesis
#12
(no author information available yet)
Elevated ascorbate levels maintain TET2 activity in HSCs and decline with differentiation.
September 1, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28841440/long-non-coding-rnas-the-novel-diagnostic-biomarkers-for-leukemia
#13
REVIEW
Shaoyun Chen, Hairong Liang, Hui Yang, Kairu Zhou, Longmei Xu, Jiaxian Liu, Bei Lai, Li Song, Hao Luo, Jianming Peng, Zhidong Liu, Yongmei Xiao, Wen Chen, Huanwen Tang
Long non-coding RNAs (LncRNAs) are a category of non-coding RNAs (ncRNAs) with a length of 200nt-100kb lacking a significant open reading frame. The study of lncRNAs is a newly established field, due in part to their capability to act as the novel biomarkers in disease. A growing body of research shows that lncRNAs may not only useful as biomarkers for the diagnosis and clinical typing and prognosis of cancers, but also as potential targets for novel therapies. Differential expression of lncRNAs has been found in leukemia in the last two years, however, the majority of the lncRNAs described here are transcripts of unknown function and their role in leukemogenesis is still unclear...
August 18, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28841206/overexpression-of-sox4-correlates-with-poor-prognosis-of-acute-myeloid-leukemia-and-is-leukemogenic-in-zebrafish
#14
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/28835438/molecular-synergy-underlies-the-co-occurrence-patterns-and-phenotype-of-npm1-mutant-acute-myeloid-leukemia
#15
Oliver M Dovey, Jonathan L Cooper, Annalisa Mupo, Carolyn S Grove, Claire Lynn, Nathalie Conte, Robert M Andrews, Suruchi Pacharne, Konstantinos Tzelepis, M S Vijayabaskar, Paul Green, Roland Rad, Mark Arends, Penny Wright, Kosuke Yusa, Allan Bradley, Ignacio Varela, George S Vassiliou
NPM1 mutations define the commonest subgroup of acute myeloid leukemia (AML) and frequently co-occur with FLT3 internal tandem duplications (ITD) or, less commonly, NRAS or KRAS mutations. Co-occurrence of mutant NPM1 with FLT3-ITD carries a significantly worse prognosis than NPM1-RAS combinations. To understand the molecular basis of these observations we compare the effects of the two combinations on hematopoiesis and leukemogenesis in knock-in mice. Early effects of these mutations on hematopoiesis show that compound Npm1(cA/+);Nras(G12D/+) or Npm1(cA);Flt3(ITD) share a number of features: Hox gene over-expression, enhanced self-renewal, expansion of hematopoietic progenitors and myeloid differentiation bias...
August 23, 2017: Blood
https://www.readbyqxmd.com/read/28821995/expression-of-the-pol-gene-of-human-endogenous-retroviruses-herv-k-and-w-in-leukemia-patients
#16
Massimiliano Bergallo, Paola Montanari, Katia Mareschi, Chiara Merlino, Massimo Berger, Ilaria Bini, Valentina Daprà, Ilaria Galliano, Franca Fagioli
The human endogenous retroviruses (HERVs) are a family of endogenous retroviruses that integrated into the germ cell DNA of primates over 30 million years ago. HERV expression seems impaired in several diseases, ranging from autoimmune to neoplastic disorders. The purpose of this study was to evaluate the overall endogenous retroviral transcription profile in bone marrow (BM) samples. A total of 30 paediatric high-risk leukaemia patients (lymphoid and myeloid malignancies) were tested for HERVs virus gene expression...
August 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28819285/phosphorylation-of-sos1-on-tyrosine-1196-promotes-its-rac-gef-activity-and-contributes-to-bcr-abl-leukemogenesis
#17
S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, S Mogjiborahman, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. While the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here, we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro, and for PDGF activation of RAC and RAC-dependent actin remodeling and cell migration...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28804122/shp2-is-required-for-bcr-abl1-induced-hematologic-neoplasia
#18
S Gu, A Sayad, G Chan, W Yang, Z Lu, C Virtanen, R A Van Etten, B G Neel
BCR-ABL1-targeting tyrosine kinase inhibitors (TKIs) have revolutionized treatment of Philadelphia chromosome-positive (Ph(+)) hematologic neoplasms. Nevertheless, acquired TKI resistance remains a major problem in chronic myeloid leukemia (CML), and TKIs are less effective against Ph(+) B-cell acute lymphoblastic leukemia (B-ALL). GAB2, a scaffolding adaptor that binds and activates SHP2, is essential for leukemogenesis by BCR-ABL1, and a GAB2 mutant lacking SHP2 binding cannot mediate leukemogenesis. Using a genetic loss-of-function approach and bone marrow transplantation models for CML and BCR-ABL1(+) B-ALL, we show that SHP2 is required for BCR-ABL1-evoked myeloid and lymphoid neoplasia...
August 14, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28794406/the-non-coding-rna-landscape-of-human-hematopoiesis-and-leukemia
#19
Adrian Schwarzer, Stephan Emmrich, Franziska Schmidt, Dominik Beck, Michelle Ng, Christina Reimer, Felix Ferdinand Adams, Sarah Grasedieck, Damian Witte, Sebastian Käbler, Jason W H Wong, Anushi Shah, Yizhou Huang, Razan Jammal, Aliaksandra Maroz, Mojca Jongen-Lavrencic, Axel Schambach, Florian Kuchenbauer, John E Pimanda, Dirk Reinhardt, Dirk Heckl, Jan-Henning Klusmann
Non-coding RNAs have emerged as crucial regulators of gene expression and cell fate decisions. However, their expression patterns and regulatory functions during normal and malignant human hematopoiesis are incompletely understood. Here we present a comprehensive resource defining the non-coding RNA landscape of the human hematopoietic system. Based on highly specific non-coding RNA expression portraits per blood cell population, we identify unique fingerprint non-coding RNAs-such as LINC00173 in granulocytes-and assign these to critical regulatory circuits involved in blood homeostasis...
August 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28794032/recombinant-origins-of-pathogenic-and-nonpathogenic-mouse-gammaretroviruses-of-polytropic-host-range
#20
Devinka Bamunusinghe, Qingping Liu, Ronald Plishka, Michael A Dolan, Matthew Skorski, Andrew J Oler, Venkat R K Yedavalli, Alicia Buckler-White, Janet W Hartley, Christine A Kozak
Ecotropic, xenotropic and polytropic mouse leukemia viruses (E-, X-, P-MLVs) exist in mice as infectious viruses and endogenous retroviruses (ERVs) inserted into mouse chromosomes. All 3 MLV subgroups are linked to leukemogenesis, which involves generation of recombinants with polytropic host range. Although P-MLVs are deemed to be the proximal agents of disease induction, few biologically characterized infectious P-MLVs have been sequenced for comparative analysis. We analyzed the complete genomes of 16 naturally occurring infectious P-MLVs, 12 of which were typed for pathogenic potential...
August 9, 2017: Journal of Virology
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