High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis
Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral...
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creator | Grywalska, Ewelina Roliński, Jacek Pasiarski, Marcin Korona-Glowniak, Izabela Maj, Maciej Surdacka, Agata Grafka, Agnieszka Stelmach-Gołdyś, Agnieszka Zgurski, Michał Góźdź, Stanisław Malm, Anna Grabarczyk, Piotr Starosławska, Elżbieta |
description | Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time |
doi_str_mv | 10.1371/journal.pone.0140178 |
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The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0140178</identifier><identifier>PMID: 26460692</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Analysis ; Antibodies, Viral - blood ; B cells ; B-Lymphocytes - immunology ; Blood ; Cancer ; Cancer genetics ; Case-Control Studies ; CD38 antigen ; Cell number ; Chronic illnesses ; Chronic lymphocytic leukemia ; Copy number ; Deoxyribonucleic acid ; Development and progression ; Distribution ; DNA ; DNA, Viral - blood ; Epstein-Barr virus ; Hematology ; Herpesvirus 4, Human - genetics ; Herpesvirus 4, Human - immunology ; Humans ; Immunology ; Immunotherapy ; Infections ; L-Lactate dehydrogenase ; Lactate dehydrogenase ; Lactic acid ; Leukemia ; Leukemia, Lymphocytic, Chronic, B-Cell - blood ; Leukemia, Lymphocytic, Chronic, B-Cell - virology ; Leukocytes (mononuclear) ; Lymphatic leukemia ; Lymphocyte receptors ; Lymphocytes ; Lymphoma ; Medical prognosis ; Middle Aged ; Multivariate Analysis ; Patients ; Peripheral blood mononuclear cells ; Phenotypes ; Probability ; Prognosis ; Proportional Hazards Models ; Viral Load ; Viruses ; World population ; ZAP-70 protein</subject><ispartof>PloS one, 2015-10, Vol.10 (10), p.e0140178-e0140178</ispartof><rights>COPYRIGHT 2015 Public Library of Science</rights><rights>2015 Grywalska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2015 Grywalska et al 2015 Grywalska et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-efc1752580f23737e19f8e717cbc5ab9df811463b05fbd7fecb8f3cbbd0077593</citedby><cites>FETCH-LOGICAL-c692t-efc1752580f23737e19f8e717cbc5ab9df811463b05fbd7fecb8f3cbbd0077593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603951/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603951/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26460692$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Pagano, Joseph S</contributor><creatorcontrib>Grywalska, Ewelina</creatorcontrib><creatorcontrib>Roliński, Jacek</creatorcontrib><creatorcontrib>Pasiarski, Marcin</creatorcontrib><creatorcontrib>Korona-Glowniak, Izabela</creatorcontrib><creatorcontrib>Maj, Maciej</creatorcontrib><creatorcontrib>Surdacka, Agata</creatorcontrib><creatorcontrib>Grafka, Agnieszka</creatorcontrib><creatorcontrib>Stelmach-Gołdyś, Agnieszka</creatorcontrib><creatorcontrib>Zgurski, Michał</creatorcontrib><creatorcontrib>Góźdź, Stanisław</creatorcontrib><creatorcontrib>Malm, Anna</creatorcontrib><creatorcontrib>Grabarczyk, Piotr</creatorcontrib><creatorcontrib>Starosławska, Elżbieta</creatorcontrib><title>High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Analysis</subject><subject>Antibodies, Viral - blood</subject><subject>B cells</subject><subject>B-Lymphocytes - immunology</subject><subject>Blood</subject><subject>Cancer</subject><subject>Cancer genetics</subject><subject>Case-Control Studies</subject><subject>CD38 antigen</subject><subject>Cell number</subject><subject>Chronic illnesses</subject><subject>Chronic lymphocytic leukemia</subject><subject>Copy number</subject><subject>Deoxyribonucleic acid</subject><subject>Development and progression</subject><subject>Distribution</subject><subject>DNA</subject><subject>DNA, Viral - blood</subject><subject>Epstein-Barr virus</subject><subject>Hematology</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Herpesvirus 4, Human - immunology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Infections</subject><subject>L-Lactate dehydrogenase</subject><subject>Lactate dehydrogenase</subject><subject>Lactic acid</subject><subject>Leukemia</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - blood</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - virology</subject><subject>Leukocytes (mononuclear)</subject><subject>Lymphatic leukemia</subject><subject>Lymphocyte receptors</subject><subject>Lymphocytes</subject><subject>Lymphoma</subject><subject>Medical prognosis</subject><subject>Middle Aged</subject><subject>Multivariate Analysis</subject><subject>Patients</subject><subject>Peripheral blood mononuclear cells</subject><subject>Phenotypes</subject><subject>Probability</subject><subject>Prognosis</subject><subject>Proportional Hazards Models</subject><subject>Viral Load</subject><subject>Viruses</subject><subject>World population</subject><subject>ZAP-70 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Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis</title><author>Grywalska, Ewelina ; Roliński, Jacek ; Pasiarski, Marcin ; Korona-Glowniak, Izabela ; Maj, Maciej ; Surdacka, Agata ; Grafka, Agnieszka ; Stelmach-Gołdyś, Agnieszka ; Zgurski, Michał ; Góźdź, Stanisław ; Malm, Anna ; Grabarczyk, Piotr ; Starosławska, Elżbieta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-efc1752580f23737e19f8e717cbc5ab9df811463b05fbd7fecb8f3cbbd0077593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Analysis</topic><topic>Antibodies, Viral - blood</topic><topic>B cells</topic><topic>B-Lymphocytes - immunology</topic><topic>Blood</topic><topic>Cancer</topic><topic>Cancer genetics</topic><topic>Case-Control 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Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Grywalska, Ewelina</au><au>Roliński, Jacek</au><au>Pasiarski, Marcin</au><au>Korona-Glowniak, Izabela</au><au>Maj, Maciej</au><au>Surdacka, Agata</au><au>Grafka, Agnieszka</au><au>Stelmach-Gołdyś, Agnieszka</au><au>Zgurski, Michał</au><au>Góźdź, Stanisław</au><au>Malm, Anna</au><au>Grabarczyk, Piotr</au><au>Starosławska, Elżbieta</au><au>Pagano, Joseph S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-10-13</date><risdate>2015</risdate><volume>10</volume><issue>10</issue><spage>e0140178</spage><epage>e0140178</epage><pages>e0140178-e0140178</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Epstein-Barr virus (EBV) is a ubiquitous γ-herpesvirus that infects more than 90% of the world population. The potential involvement of EBV in the clinical course of chronic lymphocytic leukemia (CLL) remains unexplained. The aim of this study was to determine whether EBV-DNA load in the peripheral blood mononuclear cells (PBMCs) of CLL patients may influence heterogeneity in the course of the disease. The study included peripheral blood samples from 115 previously untreated patients with CLL (54 women and 61 men) and 40 healthy controls (16 women and 24 men). We analyzed the association between the EBV-DNA load in PBMCs and the stage of the disease, adverse prognostic factors, and clinical outcome. Detectable numbers of EBV-DNA copies in PBMCs were found in 62 out of 115 CLL patients (53.91%). The EBV-DNA copy number/μg DNA was significantly higher in patients who required early implementation of treatment, presented with lymphocyte count doubling time <12 months, displayed CD38-positive or ZAP-70-positive phenotype, and with the del(11q22.3) cytogenetic abnormality. Furthermore, the EBV-DNA copy number/μg DNA showed significant positive correlation with the concentrations of lactate dehydrogenase (LDH) and beta-2-microglobulin. We have shown that in CLL patients, higher EBV-DNA copy number predicted shorter survival and shorter time to disease progression, and it was associated with other established unfavorable prognostic factors. This suggests that EBV may negatively affect the outcome of CLL.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26460692</pmid><doi>10.1371/journal.pone.0140178</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2015-10, Vol.10 (10), p.e0140178-e0140178 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1721911344 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Adult Aged Aged, 80 and over Analysis Antibodies, Viral - blood B cells B-Lymphocytes - immunology Blood Cancer Cancer genetics Case-Control Studies CD38 antigen Cell number Chronic illnesses Chronic lymphocytic leukemia Copy number Deoxyribonucleic acid Development and progression Distribution DNA DNA, Viral - blood Epstein-Barr virus Hematology Herpesvirus 4, Human - genetics Herpesvirus 4, Human - immunology Humans Immunology Immunotherapy Infections L-Lactate dehydrogenase Lactate dehydrogenase Lactic acid Leukemia Leukemia, Lymphocytic, Chronic, B-Cell - blood Leukemia, Lymphocytic, Chronic, B-Cell - virology Leukocytes (mononuclear) Lymphatic leukemia Lymphocyte receptors Lymphocytes Lymphoma Medical prognosis Middle Aged Multivariate Analysis Patients Peripheral blood mononuclear cells Phenotypes Probability Prognosis Proportional Hazards Models Viral Load Viruses World population ZAP-70 protein |
title | High Viral Loads of Epstein-Barr Virus DNA in Peripheral Blood of Patients with Chronic Lymphocytic Leukemia Associated with Unfavorable Prognosis |
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