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CML RNA sequencing

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https://www.readbyqxmd.com/read/29970515/the-potential-of-exosomes-derived-from-chronic-myelogenous-leukaemia-cells-as-a-biomarker
#1
Ka-Won Kang, Jik-Han Jung, Woojune Hur, Jaena Park, Hyunku Shin, Byeonghyeon Choi, Hyesun Jeong, Dae Sik Kim, Eun Sang Yu, Se Ryeon Lee, Hwa Jung Sung, Seok Jin Kim, Chul Won Choi, Hyun Koo Kim, Sunghoi Hong, Ji-Ho Park, Yeonho Choi, Yong Park, Byung Soo Kim
BACKGROUND/AIM: Exosomes, derived from chronic myelogenous leukaemia (CML) cells, can be used as biomarkers and new targets for the detection of the BCR-ABL transcript. This study aimed to identify these possibilities. MATERIALS AND METHODS: Human CML cell line-derived exosomes and CML-patients-derived exosomes were isolated with a size-exclusion chromatography column and ExoQuick™ exosome precipitation solution, respectively. Isolated exosomes were analysed by nested PCR to detect the BCR-ABL transcript...
July 2018: Anticancer Research
https://www.readbyqxmd.com/read/29967129/integrative-genomic-analysis-reveals-cancer-associated-mutations-at-diagnosis-of-cml-in-patients-with-high-risk-disease
#2
Susan Branford, Paul Wang, David T Yeung, Daniel Thomson, Adrian Purins, Carol Wadham, Nur Hezrin Shahrin, Justine E Marum, Nathalie Nataren, Wendy T Parker, Joel Geoghegan, Jinghua Feng, Naranie Shanmuganathan, Martin C Mueller, Christian Dietz, Doris Stangl, Zoe Donaldson, Haley Altamura, Jasmina Georgievski, Jodi Braley, Anna Brown, Christopher Hahn, Ieuan Walker, Soo-Hyun Kim, Soo-Young Choi, Sa-Hee Park, Dong-Wook Kim, Deborah L White, Agnes S M Yong, David M Ross, Hamish S Scott, Andreas W Schreiber, Timothy P Hughes
Genomic events associated with poor outcome in chronic myeloid leukemia (CML) are poorly understood. We performed whole exome sequencing, copy number variation and/or RNA-Seq for 65 patients to discover mutations at diagnosis and blast crisis (BC). Forty-six chronic phase patients with the extremes of outcome were studied at diagnosis. Cancer gene variants were detected in 15/27 patients (56%) with subsequent BC or poor outcome and in 3/19 optimal responders (16%), P=.007. Frequently mutated genes at diagnosis were ASXL1 , IKZF1 and RUNX1 The methyltransferase SETD1B was a novel recurrently mutated gene...
July 2, 2018: Blood
https://www.readbyqxmd.com/read/29772439/long-noncoding-rna-meg3-inhibits-proliferation-of-chronic-myeloid-leukemia-cells-by-sponging-microrna21
#3
Ziye Li, Lin Yang, Xiaojun Liu, Ziyuan Nie, Jianmin Luo
The long noncoding RNA (lnc) maternally expressed 3 (MEG3) is downregulated in many types of cancers. However, the relationship between lncRNA MEG3, microRNA-21 (miR-21) and chronic myeloid leukemia (CML) blast crisis is unknown. This study examined bone marrow samples from 40 CML patients and 10 healthy donors. Proliferation and apoptosis assays, real-time polymerase chain reaction (PCR), bisulfite sequencing PCR, Western blotting, luciferase assay, RNA pull-down, RNA immunoprecipitation (RIP), co-immunoprecipitation (CoIP) and Chromatin immunoprecipitation (ChIP) were performed...
August 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29725684/systemic-delivery-of-crispr-cas9-with-peg-plga-nanoparticles-for-chronic-myeloid-leukemia-targeted-therapy
#4
Yang Liu, Gui Zhao, Cong-Fei Xu, Ying-Li Luo, Zi-Dong Lu, Jun Wang
Chronic myeloid leukemia (CML), which is characterized by the Philadelphia translocation, which fuses breakpoint cluster region (BCR) sequences from chromosome 22 upstream of the Abelson murine leukemia viral oncogene homolog (ABL) on chromosome 9, requires specific and efficient treatment. The CRISPR/Cas9 system, with its mechanism of specific DNA complementary recognition by engineered guide RNA (gRNA), allows the development of novel therapeutics for CML. To achieve targeted therapy of CML with the CRISPR/Cas9 system, we encapsulated a CRISPR/Cas9 plasmid (pCas9) expressing gRNA targeting the overhanging fusion region of the BCR-ABL gene (pCas9/gBCR-ABL) with poly(ethylene glycol)-b-poly(lactic acid-co-glycolic acid) (PEG-PLGA)-based cationic lipid-assisted polymeric nanoparticles (CLANs), which specifically disrupted the CML-related BCR-ABL gene while sparing the BCR and ABL genes in normal cells...
May 29, 2018: Biomaterials Science
https://www.readbyqxmd.com/read/29284680/cd36-defines-primitive-chronic-myeloid-leukemia-cells-less-responsive-to-imatinib-but-vulnerable-to-antibody-based-therapeutic-targeting
#5
Niklas Landberg, Sofia von Palffy, Maria Askmyr, Henrik Lilljebjörn, Carl Sandén, Marianne Rissler, Satu Mustjoki, Henrik Hjorth-Hansen, Johan Richter, Helena Ågerstam, Marcus Järås, Thoas Fioretos
Tyrosine kinase inhibitors (TKIs) are highly effective for the treatment of chronic myeloid leukemia (CML), but very few patients are cured. The major drawbacks regarding TKIs are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Herein, we performed ribonucleic acid sequencing of flow-sorted primitive (CD34+ CD38low ) and progenitor (CD34+ CD38+ ) chronic phase CML cells, and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells...
March 2018: Haematologica
https://www.readbyqxmd.com/read/29165716/targeting-bcr-abl-independent-tki-resistance-in-chronic-myeloid-leukemia-by-mtor-and-autophagy-inhibition
#6
Rebecca Mitchell, Lisa E M Hopcroft, Pablo Baquero, Elaine K Allan, Kay Hewit, Daniel James, Graham Hamilton, Arunima Mukhopadhyay, Jim O'Prey, Alan Hair, Junia V Melo, Edmond Chan, Kevin M Ryan, Véronique Maguer-Satta, Brian J Druker, Richard E Clark, Subir Mitra, Pawel Herzyk, Franck E Nicolini, Paolo Salomoni, Emma Shanks, Bruno Calabretta, Tessa L Holyoake, G Vignir Helgason
Background: Imatinib and second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib have statistically significantly improved the life expectancy of chronic myeloid leukemia (CML) patients; however, resistance to TKIs remains a major clinical challenge. Although ponatinib, a third-generation TKI, improves outcomes for patients with BCR-ABL-dependent mechanisms of resistance, including the T315I mutation, a proportion of patients may have or develop BCR-ABL-independent resistance and fail ponatinib treatment...
May 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28965192/repeated-oral-exposure-to-n-%C3%AE%C2%B5-carboxymethyllysine-a-maillard-reaction-product-alleviates-gut-microbiota-dysbiosis-in-colitic-mice
#7
Nesreen ALJahdali, Pascale Gadonna-Widehem, Carine Delayre-Orthez, David Marier, Benjamin Garnier, Franck Carbonero, Pauline M Anton
BACKGROUND: Diet is suggested to participate in the etiology of inflammatory bowel diseases (IBD). Repeated exposure to Maillard reaction products (MRPs), molecules resulting from reduction reactions between amino acids and sugars during food heating, has been reported to be either potentially detrimental or beneficial to health. AIMS: The aim of this study is to determine the effect of repeated oral ingestion of N ε -carboxymethyllysine (CML), an advanced MRP, on the onset of two models of experimental IBD and on the gut microbiota composition of mice...
December 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28504724/single-cell-transcriptomics-uncovers-distinct-molecular-signatures-of-stem-cells-in-chronic-myeloid-leukemia
#8
Alice Giustacchini, Supat Thongjuea, Nikolaos Barkas, Petter S Woll, Benjamin J Povinelli, Christopher A G Booth, Paul Sopp, Ruggiero Norfo, Alba Rodriguez-Meira, Neil Ashley, Lauren Jamieson, Paresh Vyas, Kristina Anderson, Åsa Segerstolpe, Hong Qian, Ulla Olsson-Strömberg, Satu Mustjoki, Rickard Sandberg, Sten Eirik W Jacobsen, Adam J Mead
Recent advances in single-cell transcriptomics are ideally placed to unravel intratumoral heterogeneity and selective resistance of cancer stem cell (SC) subpopulations to molecularly targeted cancer therapies. However, current single-cell RNA-sequencing approaches lack the sensitivity required to reliably detect somatic mutations. We developed a method that combines high-sensitivity mutation detection with whole-transcriptome analysis of the same single cell. We applied this technique to analyze more than 2,000 SCs from patients with chronic myeloid leukemia (CML) throughout the disease course, revealing heterogeneity of CML-SCs, including the identification of a subgroup of CML-SCs with a distinct molecular signature that selectively persisted during prolonged therapy...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28480959/research-on-the-epigenetic-regulation-mechanism-of-the-ptpn6-gene-in-advanced-chronic-myeloid-leukaemia
#9
Xiaokun Zhang, Lin Yang, Xiaojun Liu, Ziyuan Nie, Xingzhe Wang, Yuxia Pan, Jianmin Luo
PTPN6, a tyrosine phosphatase protein, plays a negative role in cell signal transduction and is negatively correlated with tumour formation and growth. However, epigenetic regulation mechanism of the PTPN6 gene in advanced chronic myeloid leukaemia (CML) remains unclear. This study investigated bone marrow or blood samples from 44 CML patients and 10 healthy volunteers. KCL22 and K562 cells were cultured and treated with demethylation drugs and histone deacetylase inhibitors. Real time quantitative polymerase chain reaction (qPCR), methylation-specific PCR, bisulfite sequencing PCR, Western blotting, co-immunoprecipitation and chromatin immunoprecipitation (ChIP) was performed...
September 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28368400/interferon-%C3%AE-is-a-stat1-dependent-direct-inducer-of-bcl6-expression-in-imatinib-treated-chronic-myeloid-leukemia-cells
#10
H S Madapura, N Nagy, D Ujvari, T Kallas, M C L Kröhnke, S Amu, M Björkholm, L Stenke, P K Mandal, J S McMurray, M Keszei, L S Westerberg, H Cheng, F Xue, G Klein, E Klein, D Salamon
B-cell CLL/lymphoma 6 (BCL6) exerts oncogenic effects in several human hematopoietic malignancies including chronic myeloid leukemia (CML), where BCL6 expression was shown to be essential for CML stem cell survival and self-renewal during imatinib mesylate (IM) treatment. As several lines of evidence suggest that interferon γ (IFNγ) production in CML patients might have a central role in the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNγ modulates BCL6 expression in CML cells. Although separate IFNγ or IM treatment only slightly upregulated BCL6 expression, combined treatment induced remarkable BCL6 upregulation in CML lines and primary human CD34+ CML stem cells...
August 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28286932/hoct1-gene-expression-predict-for-optimal-response-to-imatinib-in-tunisian-patients-with-chronic-myeloid-leukemia
#11
Islem Ben Hassine, Hanene Gharbi, Ismail Soltani, Mouheb Teber, Ahlem Farrah, Hind Ben Hadj Othman, Hassiba Amouri, Hatem Bellaaj, Rayhane Ben Lakhal, Neila Ben Romdhane, Salem Abbes, Samia Menif
PURPOSE: Imatinib mesylate (IM) is considered as a highly effective therapy for chronic myeloid leukemia (CML) patients. However, a minority of patients fail to achieve optimal response due to impaired bioavailability of IM. The human organic cation transporter 1 (OCT1; SLC22A1) has been reported to be the main influx transporter involved in IM uptake into CML cells. Genetic variants and/or hOCT1 expression changes may influence IM response. In this study, we aimed to investigate the impact of both hOCT1 polymorphisms located in exon 7 and hOCT1 mRNA levels on the clinical outcome in CML patients...
April 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28079885/mirna182-regulates-percentage-of-myeloid-and-erythroid-cells-in-chronic-myeloid-leukemia
#12
Deepak Arya, Sasikala P Sachithanandan, Cecil Ross, Dasaradhi Palakodeti, Shang Li, Sudhir Krishna
The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/27854515/lncrna-uca1-contributes-to-imatinib-resistance-by-acting-as-a-cerna-against-mir-16-in-chronic-myeloid-leukemia-cells
#13
Yun Xiao, Changjie Jiao, Yiqiang Lin, Meijun Chen, Jingwen Zhang, Jiajia Wang, Zhongying Zhang
Imatinib (IM) has been applied to the chronic phase of chronic myeloid leukemia (CML) and has great benefit on the prognosis of patients with CML. The function of drug efflux mediated by multidrug resistance protein-1 (MDR1) is considered as a main reason for IM drug resistance in CML cells. However, the exact mechanisms of MDR1 modulation in IM resistance of CML cells remain unclear. In the present study, long noncoding RNA (lncRNA) UCA1 was identified as an important modulator of MDR1 by a model system of leukemia cell lines with a gradual increase of MDR1 expression and IM resistance...
January 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/27292188/adar1-activation-drives-leukemia-stem-cell-self-renewal-by-impairing-let-7-biogenesis
#14
Maria Anna Zipeto, Angela C Court, Anil Sadarangani, Nathaniel P Delos Santos, Larisa Balaian, Hye-Jung Chun, Gabriel Pineda, Sheldon R Morris, Cayla N Mason, Ifat Geron, Christian Barrett, Daniel J Goff, Russell Wall, Maurizio Pellecchia, Mark Minden, Kelly A Frazer, Marco A Marra, Leslie A Crews, Qingfei Jiang, Catriona H M Jamieson
Post-transcriptional adenosine-to-inosine RNA editing mediated by adenosine deaminase acting on RNA1 (ADAR1) promotes cancer progression and therapeutic resistance. However, ADAR1 editase-dependent mechanisms governing leukemia stem cell (LSC) generation have not been elucidated. In blast crisis chronic myeloid leukemia (BC CML), we show that increased JAK2 signaling and BCR-ABL1 amplification activate ADAR1. In a humanized BC CML mouse model, combined JAK2 and BCR-ABL1 inhibition prevents LSC self-renewal commensurate with ADAR1 downregulation...
August 4, 2016: Cell Stem Cell
https://www.readbyqxmd.com/read/27211271/next-generation-sequencing-identifies-major-dna-methylation-changes-during-progression-of-ph-chronic-myeloid-leukemia
#15
G Heller, T Topakian, C Altenberger, S Cerny-Reiterer, S Herndlhofer, B Ziegler, P Datlinger, K Byrgazov, C Bock, C Mannhalter, G Hörmann, W R Sperr, T Lion, C C Zielinski, P Valent, S Zöchbauer-Müller
Little is known about the impact of DNA methylation on the evolution/progression of Ph+ chronic myeloid leukemia (CML). We investigated the methylome of CML patients in chronic phase (CP-CML), accelerated phase (AP-CML) and blast crisis (BC-CML) as well as in controls by reduced representation bisulfite sequencing. Although only ~600 differentially methylated CpG sites were identified in samples obtained from CP-CML patients compared with controls, ~6500 differentially methylated CpG sites were found in samples from BC-CML patients...
September 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27014979/-characteristics-and-clinical-outcome-of-t315i-mutation-in-philadelphia-chromosome-positive-acute-lymphoblastic-leukemia-and-chronic-myeloid-leukemia
#16
Juan Wang, Yanli Zhang, Yingling Zu, Zhen Li, Mengjuan Li, Yongping Song
OBJECTIVE: To investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML). METHODS: The clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR)...
February 2016: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
https://www.readbyqxmd.com/read/26937281/c-myb-is-a-transcriptional-regulator-of-espl1-separase-in-bcr-abl-positive-chronic-myeloid-leukemia
#17
Wiltrud Prinzhorn, Michael Stehle, Helga Kleiner, Sabrina Ruppenthal, Martin C Müller, Wolf-Karsten Hofmann, Alice Fabarius, Wolfgang Seifarth
BACKGROUND: Genomic instability and clonal evolution are hallmarks of progressing chronic myeloid leukemia (CML). Recently, we have shown that clonal evolution and blast crisis correlate with altered expression and activity of Separase, a cysteine endopeptidase that is a mitotic key player in chromosomal segregation and centriole duplication. Hyperactivation of Separase in human hematopoietic cells has been linked to a feedback mechanism that posttranslationally stimulates Separase proteolytic activity after imatinib therapy-induced reduction of Separase protein levels...
2016: Biomarker Research
https://www.readbyqxmd.com/read/26647283/noncoding-rnas-and-their-functional-involvement-in-regulation-of-chronic-myeloid-leukemia
#18
REVIEW
Xuefei Wang, Ke Chen, Guijie Guo, Ji-Long Chen
Noncoding RNAs (ncRNAs) comprise multiple classes of transcripts that have no protein-coding ability but play critical roles as RNA regulators in various cellular processes. To date, the well-studied ncRNAs are microRNAs (miRs) that generally act as regulators of gene expression through binding to target mRNAs. Recent advances in high-throughput sequencing technologies have led to the discovery of thousands of unannotated noncoding transcripts, especially long noncoding RNAs (lncRNAs). These lncRNAs are being increasingly recognized as key regulators in diverse biological processes via a variety of mechanisms...
May 2016: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/26621726/reversion-to-an-embryonic-alternative-splicing-program-enhances-leukemia-stem-cell-self-renewal
#19
Frida Holm, Eva Hellqvist, Cayla N Mason, Shawn A Ali, Nathaniel Delos-Santos, Christian L Barrett, Hye-Jung Chun, Mark D Minden, Richard A Moore, Marco A Marra, Valeria Runza, Kelly A Frazer, Anil Sadarangani, Catriona H M Jamieson
Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse model studies demonstrated that malignant reprogramming of progenitors into self-renewing blast crisis chronic myeloid leukemia stem cells (BC LSCs) was partially driven by decreased MBNL3...
December 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26494558/functional-studies-of-mir-130a-on-the-inhibitory-pathways-of-apoptosis-in-patients-with-chronic-myeloid-leukemia
#20
X Zhu, H Zhao, Z Lin, G Zhang
The p53 mutation in chronic myeloid leukemia (CML) led to decreased overall survival and therapy resistance which was also closely correlated with the downstream proto-oncogenes BCL-2, TCL-1 and MCL-1. We in this study aimed to investigate the function of miR130a in p53 tumor suppressor signaling pathway. We performed microRNA (miRNA) expression profile analysis in CML cancer stem cells of 38 cases and extracted total RNA from peripheral blood of 143 cases. Standard curves of U6 and miRNA were made from 10-fold serial dilutions of the cDNA, which were quantified using real-time quantitative PCR with SYBR Green by ABI 7300...
December 2015: Cancer Gene Therapy
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