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miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study
The underlying mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating mic...
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| Published in: | Haematologica (Roma) 2017-04, Vol.102 (4), p.746-754 |
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| Main Authors: | , , , , , , , , , , , , , , , |
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| container_end_page | 754 |
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| container_title | Haematologica (Roma) |
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| creator | Gagez, Anne-Laure Duroux-Richard, Isabelle Leprêtre, Stéphane Orsini-Piocelle, Frédérique Letestu, Rémi De Guibert, Sophie Tuaillon, Edouard Leblond, Véronique Khalifa, Olfa Gouilleux-Gruart, Valérie Banos, Anne Tournilhac, Olivier Dupuis, Jehan Jorgensen, Christian Cartron, Guillaume Apparailly, Florence |
| description | The underlying
mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (
=0.020 and
=0.001, respectively) and with the CD20 expression on CD19
cells (
=0.0007 and |
| doi_str_mv | 10.3324/haematol.2016.153189 |
| format | article |
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mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (
=0.020 and
=0.001, respectively) and with the CD20 expression on CD19
cells (
=0.0007 and
<0.0001, respectively).
analyses of genes putatively targeted by both micro-ribonucleic acids revealed a central role of the interleukin-10 pathway and CD20 (MS4A1) family members. Interestingly, both micro-ribonucleic acids were negatively correlated with
expression, while they were positively correlated with
and
Our results identify novel circulating predictive biomarkers for rituximab-mediated lymphodepletion efficacy in chronic lymphocytic leukemia, and suggest a novel molecular mechanism responsible for the rituximab mode of action that bridges miR-125b and miR-532-3p and CD20 family members. (
).</description><identifier>ISSN: 0390-6078</identifier><identifier>EISSN: 1592-8721</identifier><identifier>DOI: 10.3324/haematol.2016.153189</identifier><identifier>PMID: 28126961</identifier><language>eng</language><publisher>Italy: Ferrata Storti Foundation</publisher><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects ; Antineoplastic Combined Chemotherapy Protocols - therapeutic use ; Biomarkers, Tumor ; Cancer ; Cluster Analysis ; Diagnosis, Differential ; Female ; Gene Expression Regulation, Leukemic ; Genotype ; Hematology ; Human health and pathology ; Humans ; Immunology ; Immunotherapy ; Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis ; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy ; Leukemia, Lymphocytic, Chronic, B-Cell - genetics ; Leukemia, Lymphocytic, Chronic, B-Cell - mortality ; Life Sciences ; Lymphocyte Depletion ; Lymphocytosis - diagnosis ; Lymphocytosis - genetics ; Male ; MicroRNAs - blood ; MicroRNAs - genetics ; Middle Aged ; Models, Biological ; Prognosis ; Rituximab - administration & dosage ; RNA Interference ; Transcriptome ; Treatment Outcome</subject><ispartof>Haematologica (Roma), 2017-04, Vol.102 (4), p.746-754</ispartof><rights>Copyright© Ferrata Storti Foundation.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright© 2017 Ferrata Storti Foundation 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c508t-f4a59d322924a91ccee6da09426621ca630ba0447ddecd68eb97e9b4426bef633</citedby><orcidid>0000-0003-0659-9635 ; 0000-0002-9438-621X ; 0000-0001-6947-8094 ; 0000-0003-1762-084X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395115/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395115/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,882,27905,27906,53772,53774</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28126961$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-01568353$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Gagez, Anne-Laure</creatorcontrib><creatorcontrib>Duroux-Richard, Isabelle</creatorcontrib><creatorcontrib>Leprêtre, Stéphane</creatorcontrib><creatorcontrib>Orsini-Piocelle, Frédérique</creatorcontrib><creatorcontrib>Letestu, Rémi</creatorcontrib><creatorcontrib>De Guibert, Sophie</creatorcontrib><creatorcontrib>Tuaillon, Edouard</creatorcontrib><creatorcontrib>Leblond, Véronique</creatorcontrib><creatorcontrib>Khalifa, Olfa</creatorcontrib><creatorcontrib>Gouilleux-Gruart, Valérie</creatorcontrib><creatorcontrib>Banos, Anne</creatorcontrib><creatorcontrib>Tournilhac, Olivier</creatorcontrib><creatorcontrib>Dupuis, Jehan</creatorcontrib><creatorcontrib>Jorgensen, Christian</creatorcontrib><creatorcontrib>Cartron, Guillaume</creatorcontrib><creatorcontrib>Apparailly, Florence</creatorcontrib><title>miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study</title><title>Haematologica (Roma)</title><addtitle>Haematologica</addtitle><description>The underlying
mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (
=0.020 and
=0.001, respectively) and with the CD20 expression on CD19
cells (
=0.0007 and
<0.0001, respectively).
analyses of genes putatively targeted by both micro-ribonucleic acids revealed a central role of the interleukin-10 pathway and CD20 (MS4A1) family members. Interestingly, both micro-ribonucleic acids were negatively correlated with
expression, while they were positively correlated with
and
Our results identify novel circulating predictive biomarkers for rituximab-mediated lymphodepletion efficacy in chronic lymphocytic leukemia, and suggest a novel molecular mechanism responsible for the rituximab mode of action that bridges miR-125b and miR-532-3p and CD20 family members. (
).</description><subject>Antineoplastic Combined Chemotherapy Protocols - adverse effects</subject><subject>Antineoplastic Combined Chemotherapy Protocols - therapeutic use</subject><subject>Biomarkers, Tumor</subject><subject>Cancer</subject><subject>Cluster Analysis</subject><subject>Diagnosis, Differential</subject><subject>Female</subject><subject>Gene Expression Regulation, Leukemic</subject><subject>Genotype</subject><subject>Hematology</subject><subject>Human health and pathology</subject><subject>Humans</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - genetics</subject><subject>Leukemia, Lymphocytic, Chronic, B-Cell - mortality</subject><subject>Life Sciences</subject><subject>Lymphocyte Depletion</subject><subject>Lymphocytosis - diagnosis</subject><subject>Lymphocytosis - genetics</subject><subject>Male</subject><subject>MicroRNAs - blood</subject><subject>MicroRNAs - genetics</subject><subject>Middle Aged</subject><subject>Models, Biological</subject><subject>Prognosis</subject><subject>Rituximab - administration & dosage</subject><subject>RNA Interference</subject><subject>Transcriptome</subject><subject>Treatment Outcome</subject><issn>0390-6078</issn><issn>1592-8721</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpdkt1u1DAQhSMEokvhDRDyJVxk8U_sxDdIq4rSlVaqhODamjiTjUsSBydZsTwUz4j3r6Jc2Z4581nHPknyltGlEDz72AB2MPl2ySlTSyYFK_SzZMGk5mmRc_Y8WVChaapoXlwlr8bxgVJOtc5fJle8YFxpxRbJn859TRmXJYG-IoeDFDwVAxkCVs5OZGqQYF0767C3e-JrEtw0_3IdlGkXJTBhRdp9NzS-wqHFyfmeuJ7YJvje2XPL7qfDHucf2DkgA0wRN41LsiK3IYIbsu57v4vlHZLNRXYfttC733BkjtNc7V8nL2poR3xzXq-T77efv93cpZv7L-ub1Sa1khZTWmcgdSU41zwDzaxFVBVQnXGlOLOgBC2BZlleVWgrVWCpc9RlFvsl1kqI62R94lYeHswQot2wNx6cORZ82BoI0VKLRkLOJaJAJYssLyxoARmva4jvniFkkfXpxBrmMr6YjcYDtE-gTzu9a8zW74wUWrL4sdfJhxOg-W_sbrUxhxplUhVCih2L2vfny4L_OeM4mc6NFtsWevTzaFiheK4kPXrMTlIb_DgGrB_ZjJpDxMwlYuYQMXOKWBx796-dx6FLpsRfP_TSfA</recordid><startdate>20170401</startdate><enddate>20170401</enddate><creator>Gagez, Anne-Laure</creator><creator>Duroux-Richard, Isabelle</creator><creator>Leprêtre, Stéphane</creator><creator>Orsini-Piocelle, Frédérique</creator><creator>Letestu, Rémi</creator><creator>De Guibert, Sophie</creator><creator>Tuaillon, Edouard</creator><creator>Leblond, Véronique</creator><creator>Khalifa, Olfa</creator><creator>Gouilleux-Gruart, Valérie</creator><creator>Banos, Anne</creator><creator>Tournilhac, Olivier</creator><creator>Dupuis, Jehan</creator><creator>Jorgensen, Christian</creator><creator>Cartron, Guillaume</creator><creator>Apparailly, Florence</creator><general>Ferrata Storti Foundation</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-0659-9635</orcidid><orcidid>https://orcid.org/0000-0002-9438-621X</orcidid><orcidid>https://orcid.org/0000-0001-6947-8094</orcidid><orcidid>https://orcid.org/0000-0003-1762-084X</orcidid></search><sort><creationdate>20170401</creationdate><title>miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. 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A French Innovative Leukemia Organization study</atitle><jtitle>Haematologica (Roma)</jtitle><addtitle>Haematologica</addtitle><date>2017-04-01</date><risdate>2017</risdate><volume>102</volume><issue>4</issue><spage>746</spage><epage>754</epage><pages>746-754</pages><issn>0390-6078</issn><eissn>1592-8721</eissn><abstract>The underlying
mechanisms of rituximab action remain incompletely understood in chronic lymphocytic leukemia. Recent data suggest that circulating micro-ribonucleic acids correlate with chronic lymphocytic leukemia progression and response to rituximab. Our study aimed at identifying circulating micro-ribonucleic acids that predict response to rituximab monotherapy in chronic lymphocytic leukemia patients. Using a hierarchical clustering of micro-ribonucleic acid expression profiles discriminating 10 untreated patients with low or high lymphocyte counts, we found 26 micro-ribonucleic acids significantly deregulated. Using individual real-time reverse transcription polymerase chain reaction, the expression levels of micro-ribonucleic acids representative of these two clusters were further validated in a larger cohort (n=61). MiR-125b and miR-532-3p were inversely correlated with rituximab-induced lymphodepletion (
=0.020 and
=0.001, respectively) and with the CD20 expression on CD19
cells (
=0.0007 and
<0.0001, respectively).
analyses of genes putatively targeted by both micro-ribonucleic acids revealed a central role of the interleukin-10 pathway and CD20 (MS4A1) family members. Interestingly, both micro-ribonucleic acids were negatively correlated with
expression, while they were positively correlated with
and
Our results identify novel circulating predictive biomarkers for rituximab-mediated lymphodepletion efficacy in chronic lymphocytic leukemia, and suggest a novel molecular mechanism responsible for the rituximab mode of action that bridges miR-125b and miR-532-3p and CD20 family members. (
).</abstract><cop>Italy</cop><pub>Ferrata Storti Foundation</pub><pmid>28126961</pmid><doi>10.3324/haematol.2016.153189</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0003-0659-9635</orcidid><orcidid>https://orcid.org/0000-0002-9438-621X</orcidid><orcidid>https://orcid.org/0000-0001-6947-8094</orcidid><orcidid>https://orcid.org/0000-0003-1762-084X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Haematologica (Roma), 2017-04, Vol.102 (4), p.746-754 |
| issn | 0390-6078 1592-8721 |
| language | eng |
| recordid | cdi_doaj_primary_oai_doaj_org_article_5a725ee3e658478ca93a42ffa0784ea4 |
| source | Freely Accessible Science Journals - check A-Z of ejournals; PubMed Central |
| subjects | Antineoplastic Combined Chemotherapy Protocols - adverse effects Antineoplastic Combined Chemotherapy Protocols - therapeutic use Biomarkers, Tumor Cancer Cluster Analysis Diagnosis, Differential Female Gene Expression Regulation, Leukemic Genotype Hematology Human health and pathology Humans Immunology Immunotherapy Leukemia, Lymphocytic, Chronic, B-Cell - diagnosis Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy Leukemia, Lymphocytic, Chronic, B-Cell - genetics Leukemia, Lymphocytic, Chronic, B-Cell - mortality Life Sciences Lymphocyte Depletion Lymphocytosis - diagnosis Lymphocytosis - genetics Male MicroRNAs - blood MicroRNAs - genetics Middle Aged Models, Biological Prognosis Rituximab - administration & dosage RNA Interference Transcriptome Treatment Outcome |
| title | miR-125b and miR-532-3p predict the efficiency of rituximab-mediated lymphodepletion in chronic lymphocytic leukemia patients. A French Innovative Leukemia Organization study |
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