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leukemia genomic

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https://www.readbyqxmd.com/read/29456553/silencing-of-iron-and-heme-related-genes-revealed-a-paramount-role-of-iron-in-the-physiology-of-the-hematophagous-vector-rhodnius-prolixus
#1
Ana B Walter-Nuno, Mabel L Taracena, Rafael D Mesquita, Pedro L Oliveira, Gabriela O Paiva-Silva
Iron is an essential element for most organisms However, free iron and heme, its complex with protoporphyrin IX, can be extremely cytotoxic, due to the production of reactive oxygen species, eventually leading to oxidative stress. Thus, eukaryotic cells control iron availability by regulating its transport, storage and excretion as well as the biosynthesis and degradation of heme. In the genome of Rhodnius prolixus , the vector of Chagas disease, we identified 36 genes related to iron and heme metabolism We performed a comprehensive analysis of these genes, including identification of homologous genes described in other insect genomes...
2018: Frontiers in Genetics
https://www.readbyqxmd.com/read/29449437/dynamic-clonal-progression-in-xenografts-of-acute-lymphoblastic-leukemia-with-intrachromosomal-amplification-of-chromosome-21
#2
Paul B Sinclair, Helen H Blair, Sarra L Ryan, Lars Buechler, Joanna Cheng, Jake Clayton, Rebecca Hanna, Shaun Hollern, Zoe Hawking, Matthew Bashton, Claire J Schwab, Lisa Jones, Lisa J Russell, Helen Marr, Peter Carey, Christina Halsey, Olaf Heidenreich, Anthony V Moorman, Christine J Harrison
Intrachromosomal amplification of chromosome 21 is a heterogeneous chromosomal rearrangement occurring in 2% of childhood precursor B-cell acute lymphoblastic leukemia. There are no cell lines with iAMP21 and these abnormalities are too complex to faithfully engineer in animal models. As a resource for future functional and pre-clinical studies, we have created xenografts from intrachromosomal amplification of chromosome 21 leukemia patient blasts and characterised them by in-vivo and ex-vivo luminescent imaging, FLOW immunophenotyping, and histological and ultrastructural analysis of bone marrow and the central nervous system...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29449436/mixed-species-rnaseq-analysis-of-human-lymphoma-cells-adhering-to-mouse-stromal-cells-identifies-a-core-gene-set-that-is-also-differentially-expressed-in-the-lymph-node-microenvironment-of-mantle-cell-lymphoma-and-chronic-lymphocytic-leukemia-patients
#3
Gustav Arvidsson, Johan Henriksson, Birgitta Sander, Anthony P Wright
A subset of hematological cancer patients is refractory to treatment or suffers relapse, due in part to minimal residual disease, whereby some cancer cells survive treatment. Cell-adhesion mediated drug resistance is an important mechanism, whereby cancer cells receive survival signals via interaction with e.g. stromal cells. No genome-wide studies of in vitro systems have yet been performed to compare gene expression in different cell subsets within a co-culture and cells grown separately. Using RNA sequencing and species-specific read mapping, we compared transcript levels in human Jeko-1 mantle cell lymphoma cells stably adhered to mouse MS-5 stromal cells or in suspension within a co-culture or cultured separately as well as in stromal cells in co-culture or in separate culture...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29449433/highly-similar-genomic-landscapes-in-monoclonal-b-cell-lymphocytosis-and-ultra-stable-chronic-lymphocytic-leukemia-with-low-frequency-of-driver-mutations
#4
Andreas Agathangelidis, Viktor Ljungström, Lydia Scarfò, Claudia Fazi, Maria Gounari, Tatjana Pandzic, Lesley-Ann Sutton, Kostas Stamatopoulos, Giovanni Tonon, Richard Rosenquist, Paolo Ghia
Despite the recent discovery of recurrent driver mutations in chronic lymphocytic leukemia, the genetic factors involved in disease onset remain largely unknown. To address this issue, we performed whole-genome sequencing in 11 individuals with monoclonal B-cell lymphocytosis, both of the low-count and high-count subtypes, and 5 patients with ultra-stable chronic lymphocytic leukemia (>10 years without progression from initial diagnosis). All three entities were indistiguishable at the genomic level exhibiting low genomic complexity and similar types of somatic mutations...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29447373/coupling-the-core-of-the-anticancer-drug-etoposide-to-an-oligonucleotide-induces-topoisomerase-ii-mediated-cleavage-at-specific-dna-sequences
#5
Lorena Infante Lara, Sabine Fenner, Steven Ratcliffe, Albert Isidro-Llobet, Michael Hann, Ben Bax, Neil Osheroff
Etoposide and other topoisomerase II-targeted drugs are important anticancer therapeutics. Unfortunately, the safe usage of these agents is limited by their indiscriminate induction of topoisomerase II-mediated DNA cleavage throughout the genome and by a lack of specificity toward cancer cells. Therefore, as a first step toward constraining the distribution of etoposide-induced DNA cleavage sites and developing sequence-specific topoisomerase II-targeted anticancer agents, we covalently coupled the core of etoposide to oligonucleotides centered on a topoisomerase II cleavage site in the PML gene...
February 13, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29446543/cyclin-dependent-kinase-inhibitor-2a-b-gene-deletions-are-markers-of-poor-prognosis-in-indian-children-with-acute-lymphoblastic-leukemia
#6
Manisha Agarwal, Sameer Bakhshi, Sadanand N Dwivedi, Madhulika Kabra, Rashmi Shukla, Rachna Seth
BACKGROUND: Cyclin dependent kinase inhibitor 2A/B (CDKN2A/B) genes are implicated in many malignancies including acute lymphoblastic leukemia (ALL). These tumor suppressor genes, with a key regulatory role in cell cycle are located on chromosome 9p21.3. Previous studies involving CDKN2A/B gene deletions have shown mixed associations with survival outcome in childhood ALL. PROCEDURE: Hundred and four newly diagnosed children with ALL (1-14 years) were enrolled in this study...
February 15, 2018: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/29440636/chronic-neutrophilic-leukemia-new-science-and-new-diagnostic-criteria
#7
REVIEW
Natasha Szuber, Ayalew Tefferi
Chronic neutrophilic leukemia (CNL) is a distinct myeloproliferative neoplasm defined by persistent, predominantly mature neutrophil proliferation, marrow granulocyte hyperplasia, and frequent splenomegaly. The seminal discovery of oncogenic driver mutations in CSF3R in the majority of patients with CNL in 2013 generated a new scientific framework for this disease as it deepened our understanding of its molecular pathogenesis, provided a biomarker for diagnosis, and rationalized management using novel targeted therapies...
February 13, 2018: Blood Cancer Journal
https://www.readbyqxmd.com/read/29439951/enhancer-dysfunction-in-leukemia
#8
Anand S Bhagwat, Bin Lu, Christopher R Vakoc
Hematopoietic cancers are often initiated by deregulation of the transcriptional machinery. Prominent among such regulators are the sequence-specific DNA-binding transcription factors (TFs), which bind to enhancer and promoter elements in the genome to control gene expression through the recruitment of cofactors. Remarkably, perturbing the function of even a single TF or cofactor can modulate the active enhancer landscape of a cell and, conversely, knowledge of the enhancer configuration can be used to discover functionally important TFs in a given cellular process...
February 9, 2018: Blood
https://www.readbyqxmd.com/read/29439661/genome-wide-scan-for-commons-snps-affecting-bovine-leukemia-virus-infection-level-in-dairy-cattle
#9
Hugo A Carignano, Dana L Roldan, María J Beribe, María A Raschia, Ariel Amadio, Juan P Nani, Gerónimo Gutierrez, Irene Alvarez, Karina Trono, Mario A Poli, Marcos M Miretti
BACKGROUND: Bovine leukemia virus (BLV) infection is omnipresent in dairy herds causing direct economic losses due to trade restrictions and lymphosarcoma-related deaths. Milk production drops and increase in the culling rate are also relevant and usually neglected. The BLV provirus persists throughout a lifetime and an inter-individual variation is observed in the level of infection (LI) in vivo. High LI is strongly correlated with disease progression and BLV transmission among herd mates...
February 13, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29438720/selenite-and-methylseleninic-acid-epigenetically-affects-distinct-gene-sets-in-myeloid-leukemia-a-genome-wide-epigenetic-analysis
#10
Prajakta Khalkar, Hani Abdulkadir Ali, Paula Codó, Nuria Díaz Argelich, Anni Martikainen, Mohsen Karimi Arzenani, Sören Lehmann, Julian Walfridsson, Johanna Ungerstedt, Aristi P Fernandes
Selenium compounds have emerged as promising chemotherapeutic agents with proposed epigenetic effects, however the mechanisms and downstream effects are yet to be studied. Here we assessed the effects of the inorganic selenium compound selenite and the organic form methylseleninic acid (MSA) in a leukemic cell line K562, on active (histone H3 lysine 9 acetylation, H3K9ac and histone H3 lysine 4 tri-methylation, H3K4me3) and repressive (histone H3 lysine 9 tri-methylation, H3K9me3) histone marks by Chromatin immunoprecipitation followed by DNA sequencing (ChIP-Seq)...
February 10, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29435155/assessment-of-a-new-genomic-classification-system-in-acute-myeloid-leukemia-with-a-normal-karyotype
#11
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Ja-Yeon Lee, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Yoo Jin Lee, Jong-Ho Won, Sung-Hyun Kim, Zhaolei Zhang, TaeHyung Kim, Dennis Dong Hwan Kim
This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29435140/triplications-of-human-chromosome-21-orthologous-regions-in-mice-result-in-expansion-of-megakaryocyte-erythroid-progenitors-and-reduction-of-granulocyte-macrophage-progenitors
#12
Chunhong Liu, Tao Yu, Zhuo Xing, Xiaoling Jiang, Yichen Li, Annie Pao, Justin Mu, Paul K Wallace, George Stoica, Andrei V Bakin, Y Eugene Yu
Individuals with Down syndrome (DS) frequently have hematopoietic abnormalities, including transient myeloproliferative disorder and acute megakaryoblastic leukemia which are often accompanied by acquired GATA1 mutations that produce a truncated protein, GATA1s. The mouse has been used for modeling DS based on the syntenic conservation between human chromosome 21 (Hsa21) and three regions in the mouse genome located on mouse chromosome 10 (Mmu10), Mmu16 and Mmu17. To assess the impact of the dosage increase of Hsa21 gene orthologs on the hematopoietic system, we characterized the related phenotype in the Dp(10)1Yey/+;Dp(16)1Yey/+;Dp(17)1Yey/+ model which carries duplications spanning the entire Hsa21 orthologous regions on Mmu10, Mmu16 and Mmu17, and the Dp(10)1Yey /+; Dp(16)1Yey /+; Dp(17)1Yey/+ ; Gata1 Yeym2 model which carries a Gata1s mutation we engineered...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434033/pdgfrb-mutation-and-tyrosine-kinase-inhibitor-resistance-in-ph-like-acute-lymphoblastic-leukemia
#13
Yingchi Zhang, Yufeng Gao, Hui Zhang, Jingliao Zhang, Fuhong He, Aleš Hnízda, Maoxiang Qian, Xiaoming Liu, Yoshihiro Gocho, Ching-Hon Pui, Tao Cheng, Qianfei Wang, Jun J Yang, Xiaofan Zhu, Xin Liu
Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) comprises of approximately 10-15% of childhood ALL cases, many of whom respond exquisitely to tyrosine kinase inhibitors (TKIs), e.g., imatinib in PDGFRB-rearranged ALL. However, some cases developed drug resistance to TKIs with mechanisms poorly understood. In this study, we identified a novel PDGFRB fusion gene, namely AGGF1-PDGFRB, and functionally characterized its oncogenic potential in vitro. Further genomic profiling of longitudinally collected samples during treatment revealed the emergence of a mutation PDGFRBC843G , which directly conferred resistance to all generations of ABL TKIs, including imatinib, dasatinib, nilotinib, and ponatinib...
February 6, 2018: Blood
https://www.readbyqxmd.com/read/29429887/assessment-of-capture-and-amplicon-based-approaches-for-the-development-of-a-targeted-next-generation-sequencing-pipeline-to-personalize-lymphoma-management
#14
Stacy S Hung, Barbara Meissner, Elizabeth A Chavez, Susana Ben-Neriah, Daisuke Ennishi, Martin R Jones, Hennady P Shulha, Fong Chun Chan, Merrill Boyle, Robert Kridel, Randy D Gascoyne, Andrew J Mungall, Marco A Marra, David W Scott, Joseph M Connors, Christian Steidl
Targeted next-generation sequencing panels are increasingly used to assess the value of gene mutations for clinical diagnostic purposes. For assay development, amplicon-based methods have been preferentially used on the basis of short preparation time and small DNA input amounts. However, capture sequencing has emerged as an alternative approach because of high testing accuracy. We compared capture hybridization and amplicon sequencing approaches using fresh-frozen and formalin-fixed, paraffin-embedded tumor samples from eight lymphoma patients...
February 7, 2018: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/29429020/leukemia-propagating-cells-demonstrate-distinctive-gene-expression-profiles-compared-with-other-cell-fractions-from-patients-with-de-novo-philadelphia-chromosome-positive-all
#15
Hong-Yan Zhao, Yang Song, Xie-Na Cao, Ya-Zhen Qin, Yue-Yun Lai, Hao Jiang, Qian Jiang, Xiao-Jun Huang, Yuan Kong
Relapse remains one of the major obstacles in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) even after allogeneic hematopoietic stem cell transplantation. The persistence of leukemia-propagating cells (LPCs) may lead to the recurrence of Ph + ALL. Using a xenograft assay, LPCs enrichment in the CD34 + CD38 - CD58 - fraction in Ph + ALL was recently identified. A further cohort study indicated that the LPCs phenotype at diagnosis was an independent risk factor for relapse of Ph + ALL...
February 10, 2018: Annals of Hematology
https://www.readbyqxmd.com/read/29428370/reinforcing-the-utility-of-chick-embryo-model-to-in-vivo-evaluate-engraftment-of-human-leukemic-stem-cells
#16
Arwa Farhat, Eiad Ali-Deeb, Amin Sulaiman, Majd Aljamali
BACKGROUND AND OBJECTIVE: Development of appropriate translational in vivo models is a prerequisite for personalized management of leukemic patients. Indeed, several immunodeficient mice models were developed for leukemias with main limitations due to their high cost, demanding management, and elongated assessment intervals. In this report, we aimed at evaluating the engraftment of CD34+ cells, isolated from an acute myeloid leukemia (AML) patient, in naturally immunodeficient chick embryo model...
February 7, 2018: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/29427646/epigenetic-deregulation-in-chronic-lymphocytic-leukemia-clinical-and-biological-impact
#17
REVIEW
Larry Mansouri, Justyna Anna Wierzbinska, Christoph Plass, Richard Rosenquist
Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic 'landscape' has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis with both biological and clinical impact. Subsequent genome-wide profiling studies revealed differential DNA methylation between CLLs and controls and in prognostics subgroups of the disease...
February 7, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29427526/nup98-bptf-gene-fusion-identified-in-primary-refractory-acute-megakaryoblastic-leukemia-of-infancy
#18
Mathieu Roussy, Mélanie Bilodeau, Loubna Jouan, Pauline Tibout, Louise Laramée, Emmanuelle Lemyre, Sophie Cardin, Camille Sauvageau, Françoise Couture, Aurélien Choblet, Natalie Patey, Patrick Gendron, Michel Duval, Pierre Teira, Josée Hébert, Brian T Wilhelm, John K Choi, Tanja A Gruber, Henrique Bittencourt, Sonia Cellot
The advent of large scale genomic sequencing technologies significantly improved the molecular classification of acute megakaryoblastic leukaemia (AMKL). AMKL represents a subset (∼10%) of high fatality pediatric acute myeloid leukemia (AML). Recurrent and mutually exclusive chimeric gene fusions associated with pediatric AMKL are found in 60-70% of cases and include RBM15-MKL1, CBFA2T3-GLIS2, NUP98-KDM5A and MLL rearrangements. In addition, another 4% of AMKL harbor NUP98 rearrangements (NUP98r), with yet undetermined fusion partners...
February 10, 2018: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/29425681/differences-in-the-internalization-of-self-inactivating-vsvg-pseudotyped-murine-leukemia-virus-based-vectors-in-human-and-murine-cells
#19
Mónica Loreto Acevedo, Francisco García-de Gracia, Camila Miranda-Cárdenas, Ricardo Soto-Rifo, Francisco Aguayo, Oscar León
Self-inactivating VSVG-pseudotyped murine leukemia virus (SIN-VSVG-MLV) has been widely used to generate stable cell lines and produce gene delivery vectors. Despite the broad cellular tropism of the VSVG-pseudotyped MLV, we observed differential viral transduction efficiency depending on the host cell type used. In order to determine the mechanism underlying these differences, we used a GFP-expressing SIN-VSVG-MLV and analyzed the major steps of viral transduction in different cell lines including human epithelial, T-lymphocytes, monocytes and murine fibroblast cells...
February 6, 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29425303/regulation-of-the-positive-transcriptional-effect-of-plzf-through-a-non-canonical-ezh2-activity
#20
Myriam Koubi, Mathilde Poplineau, Julien Vernerey, Lia N'Guyen, Guillaume Tiberi, Sylvain Garciaz, Abdessamad El-Kaoutari, Muhammad A Maqbool, Jean-Christophe Andrau, Christel Guillouf, Andrew J Saurin, Estelle Duprez
The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes. Additionally, we identify a new association between PLZF and the histone methyltransferase, EZH2 at the genomic level...
February 7, 2018: Nucleic Acids Research
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