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leukemia genomic

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https://www.readbyqxmd.com/read/29688850/first-case-of-aml-with-rare-chromosome-translocations-a-case-report-of-twins
#1
Lin Wang, Yanhua Sun, Yanli Sun, Lingbin Meng, Xin Xu
BACKGROUND: Leukemia is different from solid tumor by harboring genetic rearrangements that predict prognosis and guide treatment strategy. PML-RARA, RUNX1-RUNX1T1, and KMT2A-rearrangement are common genetic rearrangements that drive the development of acute myeloid leukemia (AML). By contrast, rare genetic rearrangements may also contribute to leukemogenesis but are less summarized. CASE PRESENTATION: Here we reported rare fusion genes ZNF717-ZNF37A, ZNF273-DGKA, and ZDHHC2-TTTY15 in a 47-year-old AML-M4 patient with FLT3 internal tandem duplication (ITD) discovered by whole genome sequencing (WGS) using the patient's healthy sibling as a sequencing control...
April 23, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29685168/role-of-bmi1-in-epithelial-ovarian-cancer-investigated-via-the-crispr-cas9-system-and-rna-sequencing
#2
Qianying Zhao, Qiuhong Qian, Dongyan Cao, Jiaxin Yang, Ting Gui, Keng Shen
BACKGROUND: B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) might be an appropriate biomarker in the management of epithelial ovarian cancer (EOC). However, the biological role of BMI1 and its relevant molecular mechanism needs further elaboration. Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system is an excellent genome-editing tool and is scarcely used in EOC studies. METHODS: We first applied CRISPR/Cas9 technique to silence BMI1 in EOC cells; thereafter we accomplished various in vivo and in vitro experiments to detect biological behaviors of ovarian cancer cells, including MTT, flow cytometry, Transwell, real-time polymerase chain reaction and western blotting assays, etc...
April 23, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29684791/the-role-of-promyelocytic-leukemia-protein-in-steatosis-associated-hepatic-tumors-related-to-chronic-hepatitis-b-virus-infection
#3
Yih-Lin Chung, Mei-Ling Wu
The persistence of hepatitis B surface antigen (HBsAg) is a risk factor for the development of steatosis-associated tumors in chronic hepatitis B virus (HBV) infection, yet little is known about the metabolic link with this factor. We correlated HBV-related pathogenesis in genetically engineered mice and human carriers with metabolic proteomics and lipogenic gene expression profiles. The immunohistochemistry showed that the promyelocytic leukemia protein (PML, a tumor suppressor involved in genome maintenance and fatty acid oxidation), being inversely influenced by the dynamic HBsAg levels from acute phase to seroclearance, appeared as a lipo-metabolic switch linking HBsAg-induced steatosis (lipogenesis) to HBsAg-lost fat-burning hepatocarcinogenesis (lipolysis)...
April 20, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29677511/an-integrated-genome-wide-crispra-approach-to-functionalize-lncrnas-in-drug-resistance
#4
Assaf C Bester, Jonathan D Lee, Alejandro Chavez, Yu-Ru Lee, Daphna Nachmani, Suhani Vora, Joshua Victor, Martin Sauvageau, Emanuele Monteleone, John L Rinn, Paolo Provero, George M Church, John G Clohessy, Pier Paolo Pandolfi
Resistance to chemotherapy plays a significant role in cancer mortality. To identify genetic units affecting sensitivity to cytarabine, the mainstay of treatment for acute myeloid leukemia (AML), we developed a comprehensive and integrated genome-wide platform based on a dual protein-coding and non-coding integrated CRISPRa screening (DICaS). Putative resistance genes were initially identified using pharmacogenetic data from 760 human pan-cancer cell lines. Subsequently, genome scale functional characterization of both coding and long non-coding RNA (lncRNA) genes by CRISPR activation was performed...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29674644/aggressive-natural-killer-cell-leukemia-mutational-landscape-and-drug-profiling-highlight-jak-stat-signaling-as-therapeutic-target
#5
Olli Dufva, Matti Kankainen, Tiina Kelkka, Nodoka Sekiguchi, Shady Adnan Awad, Samuli Eldfors, Bhagwan Yadav, Heikki Kuusanmäki, Disha Malani, Emma I Andersson, Paavo Pietarinen, Leena Saikko, Panu E Kovanen, Teija Ojala, Dean A Lee, Thomas P Loughran, Hideyuki Nakazawa, Junji Suzumiya, Ritsuro Suzuki, Young Hyeh Ko, Won Seog Kim, Shih-Sung Chuang, Tero Aittokallio, Wing C Chan, Koichi Ohshima, Fumihiro Ishida, Satu Mustjoki
Aggressive natural killer-cell (NK-cell) leukemia (ANKL) is an extremely aggressive malignancy with dismal prognosis and lack of targeted therapies. Here, we elucidate the molecular pathogenesis of ANKL using a combination of genomic and drug sensitivity profiling. We study 14 ANKL patients using whole-exome sequencing (WES) and identify mutations in STAT3 (21%) and RAS-MAPK pathway genes (21%) as well as in DDX3X (29%) and epigenetic modifiers (50%). Additional alterations include JAK-STAT copy gains and tyrosine phosphatase mutations, which we show recurrent also in extranodal NK/T-cell lymphoma, nasal type (NKTCL) through integration of public genomic data...
April 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29666114/chronic-lymphocytic-leukemia-and-mantle-cell-lymphoma-crossroads-of-genetic-and-microenvironment-interactions
#6
Xose S Puente, Pedro Jares, Elias Campo
Chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL) are two well defined entities that diverge in their basic pathogenic mechanisms and clinical evolution but they share epidemiological characteristics, cells of origin, molecular alterations, and clinical features that differ from other lymphoid neoplasms. CLL and MCL are classically considered indolent and aggressive neoplasms, respectively. However, the clinical evolution of both tumors is very heterogeneous, with subsets of patients having a stable disease for long time whereas others require immediate intervention...
April 17, 2018: Blood
https://www.readbyqxmd.com/read/29663494/phylogenetic-analysis-of-htlv-1-in-iranian-blood-donors-hiv-1-positive-patients-and-patients-with-beta-thalassemia
#7
Leila Pirayeshfard, Zohreh Sharifi, Sedigheh Amini-Kafiabad, Nasrin Haghnazari Sadaghiani
BACKGROUND: Human T-cell leukemia virus (HTLV) has been associated with various disease types. Since the discovery of the virus in 1980, seven subtypes of the virus have been identified. HTLV is widespread and endemic in some regions, such as Japan, Africa, South America, and northeast Iran. This study aimed to identify HTLV-1 genotype and also to analyze the nucleotide sequence of the LTR region in three groups, including blood donors, HIV-1+ patients, and β-thalassemia patients. MATERIALS AND METHODS: In this cross-sectional study, 2200 samples were collected from blood donors in Tehran (2000 samples), HIV-1+ patients (100 samples) and β-thalassemia patients (100 samples)...
April 16, 2018: Journal of Medical Virology
https://www.readbyqxmd.com/read/29660410/the-spatial-and-developmental-expression-of-mouse-vwa8-von-willebrand-domain-containing-protein-8
#8
Brian S Grewe, Janet E Richmond, David E Featherstone
The Drosophila gene c12.2 was isolated in a screen examining mRNA binding proteins. Drosophila c12.2 is the mouse Vwa8 homolog. Various genome-wide associated studies have linked human Vwa8 to both neurological and oncological pathologies, which include autism, bipolar disorder, comorbid migraine, and acute myeloid leukemia, however, the function and role of the VWA8 protein remain poorly understood. To further analyze the Vwa8 gene in mouse, gene structure, protein homology modeling, and gene expression patterns were examined throughout mouse development...
April 13, 2018: Gene Expression Patterns: GEP
https://www.readbyqxmd.com/read/29651845/accurate-measurement-of-formaldehyde-induced-dna-protein-crosslinks-by-high-resolution-orbitrap-mass-spectrometry
#9
Chih-Wei Liu, Xu Tian, Hadley J Hartwell, Jiapeng Leng, Liang Chi, Kun Lu, James A Swenberg
Genomic instability caused by DNA-protein crosslink (DPCs)-induced DNA damage is implicated in disease pathogenesis, aging and cancer development. The covalent linkages between DNA and protein are induced by chemical reactions catalyzed by the endogenous metabolic intermediates and exogenous agents such as aldehydes, chemotherapeutic agents, and ionizing radiation. Formaldehyde has been classified as a genotoxic carcinogen. In addition, endogenous formaldehyde-induced DPCs may increase the risks of bone marrow toxicity and leukemia...
April 13, 2018: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29650777/-mll-leukemia-induction-by-t-9-11-chromosomal-translocation-in-human-hematopoietic-stem-cells-using-genome-editing
#10
Corina Schneidawind, Johan Jeong, Dominik Schneidawind, In-Suk Kim, Jesús Duque-Afonso, Stephen Hon Kit Wong, Masayuki Iwasaki, Erin H Breese, James L Zehnder, Matthew Porteus, Michael L Cleary
Genome editing provides a potential approach to model de novo leukemogenesis in primary human hematopoietic stem and progenitor cells (HSPCs) through induction of chromosomal translocations by targeted DNA double-strand breaks. However, very low efficiency of translocations and lack of markers for translocated cells serve as barriers to their characterization and model development. Here, we used transcription activator-like effector nucleases to generate t(9;11) chromosomal translocations encoding MLL-AF9 and reciprocal AF9-MLL fusion products in CD34+ human cord blood cells...
April 24, 2018: Blood Advances
https://www.readbyqxmd.com/read/29643943/-h19-overexpression-promotes-leukemogenesis-and-predicts-unfavorable-prognosis-in-acute-myeloid-leukemia
#11
Ting-Juan Zhang, Jing-Dong Zhou, Wei Zhang, Jiang Lin, Ji-Chun Ma, Xiang-Mei Wen, Qian Yuan, Xi-Xi Li, Zi-Jun Xu, Jun Qian
Background: The long non-coding RNA H19 plays a crucial role in solid tumor initiation and progression. However, the potential role of H19 and its clinical significance in acute myeloid leukemia (AML) remain largely elusive. Methods: H19 expression was detected by qPCR, and clinical significance in AML patients was further analyzed. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) data for AML were used as validation cohorts. The roles of H19 in cell proliferation and apoptosis were determined by cell proliferation assay and flow cytometry analysis...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29642384/tracking-the-continuous-evolutionary-processes-of-an-endogenous-retrovirus-of-the-domestic-cat-erv-dc
#12
REVIEW
Junna Kawasaki, Kazuo Nishigaki
An endogenous retrovirus (ERV) is a remnant of an ancient retroviral infection in the host genome. Although most ERVs have lost their viral productivity, a few ERVs retain their replication capacity. In addition, partially inactivated ERVs can present a potential risk to the host via their encoded virulence factors or the generation of novel viruses by viral recombination. ERVs can also eventually acquire a biological function, and this ability has been a driving force of host evolution. Therefore, the presence of an ERV can be harmful or beneficial to the host...
April 6, 2018: Viruses
https://www.readbyqxmd.com/read/29626197/proteomic-and-genomic-integration-identifies-kinase-and-differentiation-determinants-of-kinase-inhibitor-sensitivity-in-leukemia-cells
#13
Pedro Casado, Edmund H Wilkes, Farideh Miraki-Moud, Marym Mohammad Hadi, Ana Rio-Machin, Vinothini Rajeeve, Rebecca Pike, Sameena Iqbal, Santiago Marfa, Nicholas Lea, Steven Best, John Gribben, Jude Fitzgibbon, Pedro R Cutillas
No abstract text is available yet for this article.
April 7, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29622796/nf%C3%AE%C2%BAb-regulates-p21-expression-and-controls-dna-damage-induced-leukemic-differentiation
#14
Claudia M Nicolae, Michael J O'Connor, Daniel Constantin, George-Lucian Moldovan
DNA damage exposure is a major modifier of cell fate in both normal and cancer tissues. In response to DNA damage, myeloid leukemia cells activate a poorly understood terminal differentiation process. Here, we show that the NFκB pathway directly activates expression of the proliferation inhibitor p21 in response to DNA damage in myeloid leukemia cells. In order to understand the role of this unexpected regulatory event, we ablated the NFκB binding site we identified in the p21 promoter, using CRISPR/Cas9-mediated genome editing...
April 6, 2018: Oncogene
https://www.readbyqxmd.com/read/29605894/ephx1-rs1051740-t-c-tyr113his-is-strongly-associated-with-acute-myeloid-leukemia-and-kmt2a-rearrangements-in-early-age
#15
Gisele Dallapicola Brisson, Bruno de Almeida Lopes, Francianne Gomes Andrade, Filipe Vicente Dos Santos Bueno, Ingrid Sardou-Cezar, Bruno Alves de Aguiar Gonçalves, Eugênia Terra-Granado, Flávio Henrique Paraguassú-Braga, Maria S Pombo-de-Oliveira
Experimental and epidemiological data have shown that acute myeloid leukemia in early-age (i-AML) originates prenatally. The risk association between transplacental exposure to benzene metabolites and i-AML might be influenced by genetic susceptibility. In this study, we investigated the relationship between genetic polymorphisms in CYP2E1, EPHX1, MPO, NQO1, GSTM1 and GSTT1 genes, and i-AML risk. The study included 101 i-AMLs and 416 healthy controls. Genomic DNA from study subjects was purified from bone marrow or peripheral blood aspirates and genotyped for genetic polymorphisms by real-time PCR allelic discrimination, Sanger sequencing and multiplex PCR...
March 31, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29601851/microrna-155-expression-and-function-in-aml-an-evolving-paradigm
#16
REVIEW
Nisha Narayan, Cameron P Bracken, Paul G Ekert
Acute myeloid leukemia (AML) arises when immature myeloid blast cells acquire multiple, recurrent genetic and epigenetic changes that results in dysregulated proliferation. Acute leukemia is the most common form of paediatric cancer, with AML accounting for ~20% of all leukemias in children. The genomic aberrations that drive AML inhibit myeloid differentiation and activate signal transduction pathways that drive proliferation. MicroRNAs, a class of small (~22 nucleotide) non-coding RNA that post-transcriptionally suppress the expression of specifically targeted transcripts, are also frequently dysregulated in AML which may prove useful for the purposes of disease classification, prognosis and future therapeutic approaches...
March 27, 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29590629/enhancer-activation-by-pharmacologic-displacement-of-lsd1-from-gfi1-induces-differentiation-in-acute-myeloid-leukemia
#17
Alba Maiques-Diaz, Gary J Spencer, James T Lynch, Filippo Ciceri, Emma L Williams, Fabio M R Amaral, Daniel H Wiseman, William J Harris, Yaoyong Li, Sudhakar Sahoo, James R Hitchin, Daniel P Mould, Emma E Fairweather, Bohdan Waszkowycz, Allan M Jordan, Duncan L Smith, Tim C P Somervaille
Pharmacologic inhibition of LSD1 promotes blast cell differentiation in acute myeloid leukemia (AML) with MLL translocations. The assumption has been that differentiation is induced through blockade of LSD1's histone demethylase activity. However, we observed that rapid, extensive, drug-induced changes in transcription occurred without genome-wide accumulation of the histone modifications targeted for demethylation by LSD1 at sites of LSD1 binding and that a demethylase-defective mutant rescued LSD1 knockdown AML cells as efficiently as wild-type protein...
March 27, 2018: Cell Reports
https://www.readbyqxmd.com/read/29589281/treatment-outcome-of-children-with-acute-lymphoblastic-leukemia-the-tokyo-children-s-cancer-study-group-tccsg-study-l04-16
#18
Hiroyuki Takahashi, Ryosuke Kajiwara, Motohiro Kato, Daisuke Hasegawa, Daisuke Tomizawa, Yasushi Noguchi, Kazutoshi Koike, Daisuke Toyama, Hiromasa Yabe, Michiko Kajiwara, Junya Fujimura, Manabu Sotomatsu, Setsuo Ota, Miho Maeda, Hiroaki Goto, Yoko Kato, Tetsuya Mori, Takeshi Inukai, Hiroyuki Shimada, Keitaro Fukushima, Chitose Ogawa, Atsushi Makimoto, Takashi Fukushima, Kentaro Ohki, Katsuyoshi Koh, Nobutaka Kiyokawa, Atsushi Manabe, Akira Ohara
The survival rate of children with acute lymphoblastic leukemia (ALL) has increased to approximately 90% after substantial progress in risk-oriented treatment strategies. Between 2005 and 2013, the Tokyo Children's Cancer Study Group (TCCSG) conducted a risk-oriented, non-randomized study, L04-16. The principal aim of this study was to assemble background characteristics and treatment outcomes, and gather genetic information on leukemic cells under central diagnosis. This report outlines the background characteristics and treatment outcomes of 1033 children with ALL treated according to a TCCSG platform...
March 27, 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29581848/aberrant-expression-of-nkl-homeobox-gene-hlx-in-hodgkin-lymphoma
#19
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Maren Kaufmann, Roderick A F MacLeod, Hans G Drexler
NKL homeobox genes are basic regulators of cell and tissue differentiation, many acting as oncogenes in T-cell leukemia. Recently, we described an hematopoietic NKL-code comprising six particular NKL homeobox genes expressed in hematopoietic stem cells and lymphoid progenitors, unmasking their physiological roles in the development of these cell types. Hodgkin lymphoma (HL) is a B-cell malignancy showing aberrant activity of several developmental genes resulting in disturbed B-cell differentiation. To examine potential concordances in abnormal lymphoid differentiation of T- and B-cell malignancies we analyzed the expression of the hematopoietic NKL-code associated genes in HL, comprising HHEX, HLX, MSX1, NKX2-3, NKX3-1 and NKX6-3...
March 6, 2018: Oncotarget
https://www.readbyqxmd.com/read/29576547/expression-specificity-and-compensation-effect-of-ash2l-1-ash2l-2-in-mouse-embryonic-stem-cells
#20
Jing Xie, Chen Fan, Jing-Long Zhang, Shi-Qiang Zhang
H3K4me3 is an important epigenetic modification that plays a critical role in maintaining self-renewal of mouse embryonic stem cells (mESCs). H3K4me3 is catalyzed mainly by the mixed lineage leukemia (MLL) methyl-transferase complex. ASH2L, a core subunit of the MLL complex, participates in regulating the open state of chromatin in mESCs. There are two isoforms of the ASH2L protein: ASH2L-1 (80 kDa), which only exists in mouse embryonic fibroblasts and ASH2L-2 (65 kDa), which is the predominant isoform in mESCs...
March 20, 2018: Yi Chuan, Hereditas
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