Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells
In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function o...
Gespeichert in:
| Veröffentlicht in: | Leukemia 2019-09, Vol.33 (9), p.2169-2182 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2182 |
|---|---|
| container_issue | 9 |
| container_start_page | 2169 |
| container_title | Leukemia |
| container_volume | 33 |
| creator | Bill, Marius Papaioannou, Dimitrios Karunasiri, Malith Kohlschmidt, Jessica Pepe, Felice Walker, Christopher J. Walker, Allison E. Brannan, Zachary Pathmanathan, Aparna Zhang, Xiaoli Mrózek, Krzysztof LaRocco, Allison Volinia, Stefano Bloomfield, Clara D. Garzon, Ramiro Dorrance, Adrienne M. |
| description | In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged |
| doi_str_mv | 10.1038/s41375-019-0429-5 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_2190493674</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A598451098</galeid><sourcerecordid>A598451098</sourcerecordid><originalsourceid>FETCH-LOGICAL-c470t-9a51201feda4c65c689c30c88cc1325dab9f968f0aa161071bf107b57a44553b3</originalsourceid><addsrcrecordid>eNp1kdFuFSEQhonR2GP1AbwxJCbGm62wCyxcnjS1mjSaGL1Glh1OqSwcYdfYty-bU7U1GhIYmO-fMPMj9JySE0o6-aYw2vW8IVQ1hLWq4Q_QhrJeNJxz-hBtiJR9I1TLjtCTUq4IWZPiMTrqiOSSM7lBX89-7jOU4lPEJo7YLdHO9WICzhDgh4kWcHI4pLjDMcXGptHX8NOHbcG-auwyA56uISQ_4gDLN5i8wWWGCVsIoTxFj5wJBZ7dnsfoy9uzz6fvmouP5-9PtxeNZT2ZG2U4bQl1MBpmBbdCKtsRK6W1tGv5aAbllJCOGEMFJT0dXN0H3hvGOO-G7hi9PtTd5_R9gTLryZf1ByZCWopuqSJMdaJnFX35F3qVllxbrlQrGZeKijvUzgTQPro0Z2PXonrLVcUoUbJSJ_-g6hrrHGyK4Hx9vyd4dUdwCSbMlyWFZR16uQ_SA2hzKiWD0_vsJ5OvNSV6tV8f7NfVfr3ar3nVvLjtbBkmGH8rfvldgfYAlJqKO8h_Wv9_1RvKf7d-</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2284589164</pqid></control><display><type>article</type><title>Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells</title><source>MEDLINE</source><source>Alma/SFX Local Collection</source><creator>Bill, Marius ; Papaioannou, Dimitrios ; Karunasiri, Malith ; Kohlschmidt, Jessica ; Pepe, Felice ; Walker, Christopher J. ; Walker, Allison E. ; Brannan, Zachary ; Pathmanathan, Aparna ; Zhang, Xiaoli ; Mrózek, Krzysztof ; LaRocco, Allison ; Volinia, Stefano ; Bloomfield, Clara D. ; Garzon, Ramiro ; Dorrance, Adrienne M.</creator><creatorcontrib>Bill, Marius ; Papaioannou, Dimitrios ; Karunasiri, Malith ; Kohlschmidt, Jessica ; Pepe, Felice ; Walker, Christopher J. ; Walker, Allison E. ; Brannan, Zachary ; Pathmanathan, Aparna ; Zhang, Xiaoli ; Mrózek, Krzysztof ; LaRocco, Allison ; Volinia, Stefano ; Bloomfield, Clara D. ; Garzon, Ramiro ; Dorrance, Adrienne M.</creatorcontrib><description>In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged <60 years) 76 older (≥60 years) adults with cytogenetically normal AML with a ‘core enriched’ (CE) gene expression signature (GES) associated with LSCs. We identified a LSC-specific signature of 111 lncRNAs that correlated strongly with the CE-GES. Among the top upregulated LSC-associated lncRNAs, we identified the lncRNA
DANCR
. Further experiments confirmed that
DANCR
is upregulated in functionally validated LSC-enriched populations.
DANCR
knock-down in LSCs resulted in decreased stem-cell renewal and quiescence. Furthermore, we showed that targeting
Dancr
in vivo using a primary murine model of AML (expressing both
Mll
partial tandem duplication/
Flt3
internal tandem duplication) prolonged the survival of mice after serial transplantation. Our data suggest that LSCs have a distinct lncRNA signature with functional relevance and therapeutic potential.</description><identifier>ISSN: 0887-6924</identifier><identifier>ISSN: 1476-5551</identifier><identifier>EISSN: 1476-5551</identifier><identifier>DOI: 10.1038/s41375-019-0429-5</identifier><identifier>PMID: 30858548</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/91 ; 631/532/71 ; 631/67/1990/283/1897 ; Acute Disease ; Acute myeloid leukemia ; Animal models ; Animals ; Cancer ; Cancer Research ; Cell Self Renewal - genetics ; Cell self-renewal ; Chemoresistance ; Chemotherapy ; Critical Care Medicine ; Deregulation ; Female ; Gene expression ; Hematology ; Humans ; Intensive ; Internal Medicine ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Leukemia, Myeloid, Acute - metabolism ; Male ; Medicine ; Medicine & Public Health ; Mice ; Middle Aged ; Myeloid leukemia ; Neoplastic Stem Cells - metabolism ; Non-coding RNA ; Oncology ; Reproduction (copying) ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Stem cell transplantation ; Stem cells ; Transplantation</subject><ispartof>Leukemia, 2019-09, Vol.33 (9), p.2169-2182</ispartof><rights>Springer Nature Limited 2019</rights><rights>COPYRIGHT 2019 Nature Publishing Group</rights><rights>2019© Springer Nature Limited 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c470t-9a51201feda4c65c689c30c88cc1325dab9f968f0aa161071bf107b57a44553b3</citedby><cites>FETCH-LOGICAL-c470t-9a51201feda4c65c689c30c88cc1325dab9f968f0aa161071bf107b57a44553b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30858548$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bill, Marius</creatorcontrib><creatorcontrib>Papaioannou, Dimitrios</creatorcontrib><creatorcontrib>Karunasiri, Malith</creatorcontrib><creatorcontrib>Kohlschmidt, Jessica</creatorcontrib><creatorcontrib>Pepe, Felice</creatorcontrib><creatorcontrib>Walker, Christopher J.</creatorcontrib><creatorcontrib>Walker, Allison E.</creatorcontrib><creatorcontrib>Brannan, Zachary</creatorcontrib><creatorcontrib>Pathmanathan, Aparna</creatorcontrib><creatorcontrib>Zhang, Xiaoli</creatorcontrib><creatorcontrib>Mrózek, Krzysztof</creatorcontrib><creatorcontrib>LaRocco, Allison</creatorcontrib><creatorcontrib>Volinia, Stefano</creatorcontrib><creatorcontrib>Bloomfield, Clara D.</creatorcontrib><creatorcontrib>Garzon, Ramiro</creatorcontrib><creatorcontrib>Dorrance, Adrienne M.</creatorcontrib><title>Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells</title><title>Leukemia</title><addtitle>Leukemia</addtitle><addtitle>Leukemia</addtitle><description>In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged <60 years) 76 older (≥60 years) adults with cytogenetically normal AML with a ‘core enriched’ (CE) gene expression signature (GES) associated with LSCs. We identified a LSC-specific signature of 111 lncRNAs that correlated strongly with the CE-GES. Among the top upregulated LSC-associated lncRNAs, we identified the lncRNA
DANCR
. Further experiments confirmed that
DANCR
is upregulated in functionally validated LSC-enriched populations.
DANCR
knock-down in LSCs resulted in decreased stem-cell renewal and quiescence. Furthermore, we showed that targeting
Dancr
in vivo using a primary murine model of AML (expressing both
Mll
partial tandem duplication/
Flt3
internal tandem duplication) prolonged the survival of mice after serial transplantation. Our data suggest that LSCs have a distinct lncRNA signature with functional relevance and therapeutic potential.</description><subject>38/91</subject><subject>631/532/71</subject><subject>631/67/1990/283/1897</subject><subject>Acute Disease</subject><subject>Acute myeloid leukemia</subject><subject>Animal models</subject><subject>Animals</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Cell Self Renewal - genetics</subject><subject>Cell self-renewal</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Critical Care Medicine</subject><subject>Deregulation</subject><subject>Female</subject><subject>Gene expression</subject><subject>Hematology</subject><subject>Humans</subject><subject>Intensive</subject><subject>Internal Medicine</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Myeloid leukemia</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Non-coding RNA</subject><subject>Oncology</subject><subject>Reproduction (copying)</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Transplantation</subject><issn>0887-6924</issn><issn>1476-5551</issn><issn>1476-5551</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kdFuFSEQhonR2GP1AbwxJCbGm62wCyxcnjS1mjSaGL1Glh1OqSwcYdfYty-bU7U1GhIYmO-fMPMj9JySE0o6-aYw2vW8IVQ1hLWq4Q_QhrJeNJxz-hBtiJR9I1TLjtCTUq4IWZPiMTrqiOSSM7lBX89-7jOU4lPEJo7YLdHO9WICzhDgh4kWcHI4pLjDMcXGptHX8NOHbcG-auwyA56uISQ_4gDLN5i8wWWGCVsIoTxFj5wJBZ7dnsfoy9uzz6fvmouP5-9PtxeNZT2ZG2U4bQl1MBpmBbdCKtsRK6W1tGv5aAbllJCOGEMFJT0dXN0H3hvGOO-G7hi9PtTd5_R9gTLryZf1ByZCWopuqSJMdaJnFX35F3qVllxbrlQrGZeKijvUzgTQPro0Z2PXonrLVcUoUbJSJ_-g6hrrHGyK4Hx9vyd4dUdwCSbMlyWFZR16uQ_SA2hzKiWD0_vsJ5OvNSV6tV8f7NfVfr3ar3nVvLjtbBkmGH8rfvldgfYAlJqKO8h_Wv9_1RvKf7d-</recordid><startdate>20190901</startdate><enddate>20190901</enddate><creator>Bill, Marius</creator><creator>Papaioannou, Dimitrios</creator><creator>Karunasiri, Malith</creator><creator>Kohlschmidt, Jessica</creator><creator>Pepe, Felice</creator><creator>Walker, Christopher J.</creator><creator>Walker, Allison E.</creator><creator>Brannan, Zachary</creator><creator>Pathmanathan, Aparna</creator><creator>Zhang, Xiaoli</creator><creator>Mrózek, Krzysztof</creator><creator>LaRocco, Allison</creator><creator>Volinia, Stefano</creator><creator>Bloomfield, Clara D.</creator><creator>Garzon, Ramiro</creator><creator>Dorrance, Adrienne M.</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</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>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T5</scope><scope>7T7</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20190901</creationdate><title>Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells</title><author>Bill, Marius ; Papaioannou, Dimitrios ; Karunasiri, Malith ; Kohlschmidt, Jessica ; Pepe, Felice ; Walker, Christopher J. ; Walker, Allison E. ; Brannan, Zachary ; Pathmanathan, Aparna ; Zhang, Xiaoli ; Mrózek, Krzysztof ; LaRocco, Allison ; Volinia, Stefano ; Bloomfield, Clara D. ; Garzon, Ramiro ; Dorrance, Adrienne M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c470t-9a51201feda4c65c689c30c88cc1325dab9f968f0aa161071bf107b57a44553b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>38/91</topic><topic>631/532/71</topic><topic>631/67/1990/283/1897</topic><topic>Acute Disease</topic><topic>Acute myeloid leukemia</topic><topic>Animal models</topic><topic>Animals</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Cell Self Renewal - genetics</topic><topic>Cell self-renewal</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Critical Care Medicine</topic><topic>Deregulation</topic><topic>Female</topic><topic>Gene expression</topic><topic>Hematology</topic><topic>Humans</topic><topic>Intensive</topic><topic>Internal Medicine</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Myeloid leukemia</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Non-coding RNA</topic><topic>Oncology</topic><topic>Reproduction (copying)</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - genetics</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bill, Marius</creatorcontrib><creatorcontrib>Papaioannou, Dimitrios</creatorcontrib><creatorcontrib>Karunasiri, Malith</creatorcontrib><creatorcontrib>Kohlschmidt, Jessica</creatorcontrib><creatorcontrib>Pepe, Felice</creatorcontrib><creatorcontrib>Walker, Christopher J.</creatorcontrib><creatorcontrib>Walker, Allison E.</creatorcontrib><creatorcontrib>Brannan, Zachary</creatorcontrib><creatorcontrib>Pathmanathan, Aparna</creatorcontrib><creatorcontrib>Zhang, Xiaoli</creatorcontrib><creatorcontrib>Mrózek, Krzysztof</creatorcontrib><creatorcontrib>LaRocco, Allison</creatorcontrib><creatorcontrib>Volinia, Stefano</creatorcontrib><creatorcontrib>Bloomfield, Clara D.</creatorcontrib><creatorcontrib>Garzon, Ramiro</creatorcontrib><creatorcontrib>Dorrance, Adrienne M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</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>MEDLINE - Academic</collection><jtitle>Leukemia</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bill, Marius</au><au>Papaioannou, Dimitrios</au><au>Karunasiri, Malith</au><au>Kohlschmidt, Jessica</au><au>Pepe, Felice</au><au>Walker, Christopher J.</au><au>Walker, Allison E.</au><au>Brannan, Zachary</au><au>Pathmanathan, Aparna</au><au>Zhang, Xiaoli</au><au>Mrózek, Krzysztof</au><au>LaRocco, Allison</au><au>Volinia, Stefano</au><au>Bloomfield, Clara D.</au><au>Garzon, Ramiro</au><au>Dorrance, Adrienne M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells</atitle><jtitle>Leukemia</jtitle><stitle>Leukemia</stitle><addtitle>Leukemia</addtitle><date>2019-09-01</date><risdate>2019</risdate><volume>33</volume><issue>9</issue><spage>2169</spage><epage>2182</epage><pages>2169-2182</pages><issn>0887-6924</issn><issn>1476-5551</issn><eissn>1476-5551</eissn><abstract>In acute myeloid leukemia (AML), novel therapies are needed to target not only the rapidly dividing AML blasts but also the distinct population of leukemia stem cells (LSCs), which have abnormal self-renewal capacity and increased chemotherapy resistance. Elucidation of the expression and function of deregulated genes in LSCs is critical to specifically target LSCs and may consequently lead to improving outcomes of AML patients. Here, we correlated long non-coding RNA (lncRNA) expression profiles obtained from two RNA-seq datasets of 375 younger (aged <60 years) 76 older (≥60 years) adults with cytogenetically normal AML with a ‘core enriched’ (CE) gene expression signature (GES) associated with LSCs. We identified a LSC-specific signature of 111 lncRNAs that correlated strongly with the CE-GES. Among the top upregulated LSC-associated lncRNAs, we identified the lncRNA
DANCR
. Further experiments confirmed that
DANCR
is upregulated in functionally validated LSC-enriched populations.
DANCR
knock-down in LSCs resulted in decreased stem-cell renewal and quiescence. Furthermore, we showed that targeting
Dancr
in vivo using a primary murine model of AML (expressing both
Mll
partial tandem duplication/
Flt3
internal tandem duplication) prolonged the survival of mice after serial transplantation. Our data suggest that LSCs have a distinct lncRNA signature with functional relevance and therapeutic potential.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30858548</pmid><doi>10.1038/s41375-019-0429-5</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0887-6924 |
| ispartof | Leukemia, 2019-09, Vol.33 (9), p.2169-2182 |
| issn | 0887-6924 1476-5551 1476-5551 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2190493674 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | 38/91 631/532/71 631/67/1990/283/1897 Acute Disease Acute myeloid leukemia Animal models Animals Cancer Cancer Research Cell Self Renewal - genetics Cell self-renewal Chemoresistance Chemotherapy Critical Care Medicine Deregulation Female Gene expression Hematology Humans Intensive Internal Medicine Leukemia Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - metabolism Male Medicine Medicine & Public Health Mice Middle Aged Myeloid leukemia Neoplastic Stem Cells - metabolism Non-coding RNA Oncology Reproduction (copying) Ribonucleic acid RNA RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Stem cell transplantation Stem cells Transplantation |
| title | Expression and functional relevance of long non-coding RNAs in acute myeloid leukemia stem cells |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T20%3A11%3A24IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Expression%20and%20functional%20relevance%20of%20long%20non-coding%20RNAs%20in%20acute%20myeloid%20leukemia%20stem%20cells&rft.jtitle=Leukemia&rft.au=Bill,%20Marius&rft.date=2019-09-01&rft.volume=33&rft.issue=9&rft.spage=2169&rft.epage=2182&rft.pages=2169-2182&rft.issn=0887-6924&rft.eissn=1476-5551&rft_id=info:doi/10.1038/s41375-019-0429-5&rft_dat=%3Cgale_proqu%3EA598451098%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2284589164&rft_id=info:pmid/30858548&rft_galeid=A598451098&rfr_iscdi=true |