Tracking the extramedullary PML-RARα-positive cell reservoirs in a preclinical model: Biomarker of long-term drug efficacy
Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene–specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic ac...
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| Veröffentlicht in: | Molecular and cellular probes 2013-02, Vol.27 (1), p.1-5 |
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| container_title | Molecular and cellular probes |
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| creator | Pokorna, Katerina Le Pogam, Carole Chopin, Martine Balitrand, Nicole Reboul, Murielle Cassinat, Bruno Chomienne, Christine Padua, Rose Ann Pla, Marika |
| description | Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene–specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) oncogene. Kaplan–Meier survival analysis according to the peripheral blood PML-RARα normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p |
| doi_str_mv | 10.1016/j.mcp.2012.08.001 |
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Kaplan–Meier survival analysis according to the peripheral blood PML-RARα normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p < 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RARα-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RARα. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RARα-positive cell reservoirs such as the brain may persist and be involved in relapses.</description><identifier>ISSN: 0890-8508</identifier><identifier>EISSN: 1096-1194</identifier><identifier>DOI: 10.1016/j.mcp.2012.08.001</identifier><identifier>PMID: 22906630</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animal model ; Animals ; APL ; ATRA ; Brain - cytology ; Gene Dosage ; Immunotherapy ; Kaplan-Meier Estimate ; Leukemia, Promyelocytic, Acute - mortality ; Leukemia, Promyelocytic, Acute - therapy ; Mice ; Mice, Transgenic ; MRD ; Neoplasm Proteins - therapeutic use ; Oncogene Proteins, Fusion - genetics ; Oncogene Proteins, Fusion - immunology ; Oncogene Proteins, Fusion - metabolism ; RT-qPCR ; Spleen - cytology ; Treatment Outcome ; Tretinoin - therapeutic use ; Vaccination ; Vaccines, DNA - therapeutic use</subject><ispartof>Molecular and cellular probes, 2013-02, Vol.27 (1), p.1-5</ispartof><rights>2012 Elsevier Ltd</rights><rights>Copyright © 2012 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-28a74aa56402fd6ef08131aa6472c2a7f45687536f4af06b750310575fe3a2763</citedby><cites>FETCH-LOGICAL-c353t-28a74aa56402fd6ef08131aa6472c2a7f45687536f4af06b750310575fe3a2763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mcp.2012.08.001$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22906630$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pokorna, Katerina</creatorcontrib><creatorcontrib>Le Pogam, Carole</creatorcontrib><creatorcontrib>Chopin, Martine</creatorcontrib><creatorcontrib>Balitrand, Nicole</creatorcontrib><creatorcontrib>Reboul, Murielle</creatorcontrib><creatorcontrib>Cassinat, Bruno</creatorcontrib><creatorcontrib>Chomienne, Christine</creatorcontrib><creatorcontrib>Padua, Rose Ann</creatorcontrib><creatorcontrib>Pla, Marika</creatorcontrib><title>Tracking the extramedullary PML-RARα-positive cell reservoirs in a preclinical model: Biomarker of long-term drug efficacy</title><title>Molecular and cellular probes</title><addtitle>Mol Cell Probes</addtitle><description>Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene–specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) oncogene. Kaplan–Meier survival analysis according to the peripheral blood PML-RARα normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p < 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RARα-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RARα. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RARα-positive cell reservoirs such as the brain may persist and be involved in relapses.</description><subject>Animal model</subject><subject>Animals</subject><subject>APL</subject><subject>ATRA</subject><subject>Brain - cytology</subject><subject>Gene Dosage</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Leukemia, Promyelocytic, Acute - mortality</subject><subject>Leukemia, Promyelocytic, Acute - therapy</subject><subject>Mice</subject><subject>Mice, Transgenic</subject><subject>MRD</subject><subject>Neoplasm Proteins - therapeutic use</subject><subject>Oncogene Proteins, Fusion - genetics</subject><subject>Oncogene Proteins, Fusion - immunology</subject><subject>Oncogene Proteins, Fusion - metabolism</subject><subject>RT-qPCR</subject><subject>Spleen - cytology</subject><subject>Treatment Outcome</subject><subject>Tretinoin - therapeutic use</subject><subject>Vaccination</subject><subject>Vaccines, DNA - therapeutic use</subject><issn>0890-8508</issn><issn>1096-1194</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1u1DAUhS0EokPhAdggL9kkXDuJ48CqrfipNKioKmvLda4HT5042MmIEU_VF-GZ8GhalqzO5jtHOh8hrxmUDJh4ty0HM5UcGC9BlgDsCVkx6ETBWFc_JSuQHRSyAXlCXqS0BYCuBvmcnHDegRAVrMjvm6jNnRs3dP6BFH_NUQ_YL97ruKffvq6L67PrP_fFFJKb3Q6pQe9pxIRxF1xM1I1U0ymi8W50Rns6hB79e3ruwqDjHUYaLPVh3BQzxoH2cdlQtDajZv-SPLPaJ3z1kKfk-6ePNxdfivXV58uLs3VhqqaaCy51W2vdiBq47QVakKxiWou65Ybr1taNkG1TCVtrC-K2baBi0LSNxUrzVlSn5O1xd4rh54JpVoNLhyN6xLAkxZgUXZPt8IyyI2piSCmiVVN0-cheMVAH52qrsnN1cK5Aquw8d948zC-32d2_xqPkDHw4AphP7hxGlYzD0WDvsrhZ9cH9Z_4vqHqStg</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Pokorna, Katerina</creator><creator>Le Pogam, Carole</creator><creator>Chopin, Martine</creator><creator>Balitrand, Nicole</creator><creator>Reboul, Murielle</creator><creator>Cassinat, Bruno</creator><creator>Chomienne, Christine</creator><creator>Padua, Rose Ann</creator><creator>Pla, Marika</creator><general>Elsevier Ltd</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></search><sort><creationdate>201302</creationdate><title>Tracking the extramedullary PML-RARα-positive cell reservoirs in a preclinical model: Biomarker of long-term drug efficacy</title><author>Pokorna, Katerina ; Le Pogam, Carole ; Chopin, Martine ; Balitrand, Nicole ; Reboul, Murielle ; Cassinat, Bruno ; Chomienne, Christine ; Padua, Rose Ann ; Pla, Marika</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-28a74aa56402fd6ef08131aa6472c2a7f45687536f4af06b750310575fe3a2763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Animal model</topic><topic>Animals</topic><topic>APL</topic><topic>ATRA</topic><topic>Brain - cytology</topic><topic>Gene Dosage</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Leukemia, Promyelocytic, Acute - mortality</topic><topic>Leukemia, Promyelocytic, Acute - therapy</topic><topic>Mice</topic><topic>Mice, Transgenic</topic><topic>MRD</topic><topic>Neoplasm Proteins - therapeutic use</topic><topic>Oncogene Proteins, Fusion - genetics</topic><topic>Oncogene Proteins, Fusion - immunology</topic><topic>Oncogene Proteins, Fusion - metabolism</topic><topic>RT-qPCR</topic><topic>Spleen - cytology</topic><topic>Treatment Outcome</topic><topic>Tretinoin - therapeutic use</topic><topic>Vaccination</topic><topic>Vaccines, DNA - therapeutic use</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pokorna, Katerina</creatorcontrib><creatorcontrib>Le Pogam, Carole</creatorcontrib><creatorcontrib>Chopin, Martine</creatorcontrib><creatorcontrib>Balitrand, Nicole</creatorcontrib><creatorcontrib>Reboul, Murielle</creatorcontrib><creatorcontrib>Cassinat, Bruno</creatorcontrib><creatorcontrib>Chomienne, Christine</creatorcontrib><creatorcontrib>Padua, Rose Ann</creatorcontrib><creatorcontrib>Pla, Marika</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular probes</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pokorna, Katerina</au><au>Le Pogam, Carole</au><au>Chopin, Martine</au><au>Balitrand, Nicole</au><au>Reboul, Murielle</au><au>Cassinat, Bruno</au><au>Chomienne, Christine</au><au>Padua, Rose Ann</au><au>Pla, Marika</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tracking the extramedullary PML-RARα-positive cell reservoirs in a preclinical model: Biomarker of long-term drug efficacy</atitle><jtitle>Molecular and cellular probes</jtitle><addtitle>Mol Cell Probes</addtitle><date>2013-02</date><risdate>2013</risdate><volume>27</volume><issue>1</issue><spage>1</spage><epage>5</epage><pages>1-5</pages><issn>0890-8508</issn><eissn>1096-1194</eissn><abstract>Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene–specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) oncogene. Kaplan–Meier survival analysis according to the peripheral blood PML-RARα normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p < 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RARα-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RARα. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RARα-positive cell reservoirs such as the brain may persist and be involved in relapses.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>22906630</pmid><doi>10.1016/j.mcp.2012.08.001</doi><tpages>5</tpages></addata></record> |
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| subjects | Animal model Animals APL ATRA Brain - cytology Gene Dosage Immunotherapy Kaplan-Meier Estimate Leukemia, Promyelocytic, Acute - mortality Leukemia, Promyelocytic, Acute - therapy Mice Mice, Transgenic MRD Neoplasm Proteins - therapeutic use Oncogene Proteins, Fusion - genetics Oncogene Proteins, Fusion - immunology Oncogene Proteins, Fusion - metabolism RT-qPCR Spleen - cytology Treatment Outcome Tretinoin - therapeutic use Vaccination Vaccines, DNA - therapeutic use |
| title | Tracking the extramedullary PML-RARα-positive cell reservoirs in a preclinical model: Biomarker of long-term drug efficacy |
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