Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML
Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied...
Gespeichert in:
| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2010-03, Vol.327 (5973), p.1650-1653 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1653 |
|---|---|
| container_issue | 5973 |
| container_start_page | 1650 |
| container_title | Science (American Association for the Advancement of Science) |
| container_volume | 327 |
| creator | Wang, Yingzi Krivtsov, Andrei V Sinha, Amit U North, Trista E Goessling, Wolfram Feng, Zhaohui Zon, Leonard I Armstrong, Scott A |
| description | Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/β-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/β-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of β-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. β-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/β-catenin pathway may represent a new therapeutic opportunity in AML. |
| doi_str_mv | 10.1126/science.1186624 |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3084586</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20339075</sourcerecordid><originalsourceid>FETCH-LOGICAL-c446t-c01a8bbac75e26e8f4ba800ae48b34714db18abd8e7485ffd19c6e6ffa7f45143</originalsourceid><addsrcrecordid>eNpVkMtuFDEQRS0EIpPAmh14w7KZ8qPd7g1SNLwiDQKRRCytanc509CPwe4Jym_lQ_gmHM0QYGXZ99Qp6zL2TMArIaRZJt_R6ClfrDFSP2ALAXVZ1BLUQ7YAUKawUJVH7DilbwA5q9VjdpRjVef3Bbv4Os7LX7fFCmcau5F_xnnzE2_4WeJf6Meui9TyMEU-b4i_oWvqp-1A48ynwNe0-05Dh_x8poGvqO8Tz4bTj-sn7FHAPtHTw3nCLt-9vVh9KNaf3p-tTteF19rMhQeBtmnQVyVJQzboBi0AkraN0pXQbSMsNq2lStsyhFbU3pAJAaugS6HVCXu99253zUCtzx-L2Ltt7AaMN27Czv2fjN3GXU3XToHVpTVZsNwLfJxSihTuZwW4u4LdoWB3KDhPPP935T3_p9EMvDwAmDz2IeLou_SXk6WBWt2JXuy5gJPDq5iZy3MJQoGwEkBK9RuQ6pBD</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML</title><source>MEDLINE</source><source>JSTOR Archive Collection A-Z Listing</source><source>American Association for the Advancement of Science</source><creator>Wang, Yingzi ; Krivtsov, Andrei V ; Sinha, Amit U ; North, Trista E ; Goessling, Wolfram ; Feng, Zhaohui ; Zon, Leonard I ; Armstrong, Scott A</creator><creatorcontrib>Wang, Yingzi ; Krivtsov, Andrei V ; Sinha, Amit U ; North, Trista E ; Goessling, Wolfram ; Feng, Zhaohui ; Zon, Leonard I ; Armstrong, Scott A</creatorcontrib><description>Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/β-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/β-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of β-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. β-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/β-catenin pathway may represent a new therapeutic opportunity in AML.</description><identifier>ISSN: 0036-8075</identifier><identifier>EISSN: 1095-9203</identifier><identifier>DOI: 10.1126/science.1186624</identifier><identifier>PMID: 20339075</identifier><identifier>CODEN: SCIEAS</identifier><language>eng</language><publisher>Washington, DC: American Association for the Advancement of Science</publisher><subject>Animals ; beta Catenin - metabolism ; Biological and medical sciences ; Cell Proliferation ; Cell Transformation, Neoplastic ; Genes, Homeobox ; Granulocyte-Macrophage Progenitor Cells - metabolism ; Granulocyte-Macrophage Progenitor Cells - pathology ; Hematologic and hematopoietic diseases ; Hematopoietic Stem Cells - metabolism ; Hematopoietic Stem Cells - pathology ; Homeodomain Proteins - genetics ; Indomethacin - pharmacology ; Leukemia, Myeloid, Acute - metabolism ; Leukemia, Myeloid, Acute - pathology ; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis ; Medical sciences ; Mice ; Mice, Inbred C57BL ; Myeloid Ecotropic Viral Integration Site 1 Protein ; Neoplasm Proteins - genetics ; Neoplastic Stem Cells - pathology ; Signal Transduction ; Transduction, Genetic ; Wnt Proteins - metabolism</subject><ispartof>Science (American Association for the Advancement of Science), 2010-03, Vol.327 (5973), p.1650-1653</ispartof><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-c01a8bbac75e26e8f4ba800ae48b34714db18abd8e7485ffd19c6e6ffa7f45143</citedby><cites>FETCH-LOGICAL-c446t-c01a8bbac75e26e8f4ba800ae48b34714db18abd8e7485ffd19c6e6ffa7f45143</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,2884,2885,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22560934$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20339075$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Yingzi</creatorcontrib><creatorcontrib>Krivtsov, Andrei V</creatorcontrib><creatorcontrib>Sinha, Amit U</creatorcontrib><creatorcontrib>North, Trista E</creatorcontrib><creatorcontrib>Goessling, Wolfram</creatorcontrib><creatorcontrib>Feng, Zhaohui</creatorcontrib><creatorcontrib>Zon, Leonard I</creatorcontrib><creatorcontrib>Armstrong, Scott A</creatorcontrib><title>Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/β-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/β-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of β-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. β-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/β-catenin pathway may represent a new therapeutic opportunity in AML.</description><subject>Animals</subject><subject>beta Catenin - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation</subject><subject>Cell Transformation, Neoplastic</subject><subject>Genes, Homeobox</subject><subject>Granulocyte-Macrophage Progenitor Cells - metabolism</subject><subject>Granulocyte-Macrophage Progenitor Cells - pathology</subject><subject>Hematologic and hematopoietic diseases</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Hematopoietic Stem Cells - pathology</subject><subject>Homeodomain Proteins - genetics</subject><subject>Indomethacin - pharmacology</subject><subject>Leukemia, Myeloid, Acute - metabolism</subject><subject>Leukemia, Myeloid, Acute - pathology</subject><subject>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Myeloid Ecotropic Viral Integration Site 1 Protein</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neoplastic Stem Cells - pathology</subject><subject>Signal Transduction</subject><subject>Transduction, Genetic</subject><subject>Wnt Proteins - metabolism</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkMtuFDEQRS0EIpPAmh14w7KZ8qPd7g1SNLwiDQKRRCytanc509CPwe4Jym_lQ_gmHM0QYGXZ99Qp6zL2TMArIaRZJt_R6ClfrDFSP2ALAXVZ1BLUQ7YAUKawUJVH7DilbwA5q9VjdpRjVef3Bbv4Os7LX7fFCmcau5F_xnnzE2_4WeJf6Meui9TyMEU-b4i_oWvqp-1A48ynwNe0-05Dh_x8poGvqO8Tz4bTj-sn7FHAPtHTw3nCLt-9vVh9KNaf3p-tTteF19rMhQeBtmnQVyVJQzboBi0AkraN0pXQbSMsNq2lStsyhFbU3pAJAaugS6HVCXu99253zUCtzx-L2Ltt7AaMN27Czv2fjN3GXU3XToHVpTVZsNwLfJxSihTuZwW4u4LdoWB3KDhPPP935T3_p9EMvDwAmDz2IeLou_SXk6WBWt2JXuy5gJPDq5iZy3MJQoGwEkBK9RuQ6pBD</recordid><startdate>20100326</startdate><enddate>20100326</enddate><creator>Wang, Yingzi</creator><creator>Krivtsov, Andrei V</creator><creator>Sinha, Amit U</creator><creator>North, Trista E</creator><creator>Goessling, Wolfram</creator><creator>Feng, Zhaohui</creator><creator>Zon, Leonard I</creator><creator>Armstrong, Scott A</creator><general>American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</scope><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>5PM</scope></search><sort><creationdate>20100326</creationdate><title>Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML</title><author>Wang, Yingzi ; Krivtsov, Andrei V ; Sinha, Amit U ; North, Trista E ; Goessling, Wolfram ; Feng, Zhaohui ; Zon, Leonard I ; Armstrong, Scott A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-c01a8bbac75e26e8f4ba800ae48b34714db18abd8e7485ffd19c6e6ffa7f45143</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>beta Catenin - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation</topic><topic>Cell Transformation, Neoplastic</topic><topic>Genes, Homeobox</topic><topic>Granulocyte-Macrophage Progenitor Cells - metabolism</topic><topic>Granulocyte-Macrophage Progenitor Cells - pathology</topic><topic>Hematologic and hematopoietic diseases</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Hematopoietic Stem Cells - pathology</topic><topic>Homeodomain Proteins - genetics</topic><topic>Indomethacin - pharmacology</topic><topic>Leukemia, Myeloid, Acute - metabolism</topic><topic>Leukemia, Myeloid, Acute - pathology</topic><topic>Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Myeloid Ecotropic Viral Integration Site 1 Protein</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neoplastic Stem Cells - pathology</topic><topic>Signal Transduction</topic><topic>Transduction, Genetic</topic><topic>Wnt Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Yingzi</creatorcontrib><creatorcontrib>Krivtsov, Andrei V</creatorcontrib><creatorcontrib>Sinha, Amit U</creatorcontrib><creatorcontrib>North, Trista E</creatorcontrib><creatorcontrib>Goessling, Wolfram</creatorcontrib><creatorcontrib>Feng, Zhaohui</creatorcontrib><creatorcontrib>Zon, Leonard I</creatorcontrib><creatorcontrib>Armstrong, Scott A</creatorcontrib><collection>AGRIS</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Science (American Association for the Advancement of Science)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Yingzi</au><au>Krivtsov, Andrei V</au><au>Sinha, Amit U</au><au>North, Trista E</au><au>Goessling, Wolfram</au><au>Feng, Zhaohui</au><au>Zon, Leonard I</au><au>Armstrong, Scott A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML</atitle><jtitle>Science (American Association for the Advancement of Science)</jtitle><addtitle>Science</addtitle><date>2010-03-26</date><risdate>2010</risdate><volume>327</volume><issue>5973</issue><spage>1650</spage><epage>1653</epage><pages>1650-1653</pages><issn>0036-8075</issn><eissn>1095-9203</eissn><coden>SCIEAS</coden><abstract>Leukemia stem cells (LSCs) are capable of limitless self-renewal and are responsible for the maintenance of leukemia. Because selective eradication of LSCs could offer substantial therapeutic benefit, there is interest in identifying the signaling pathways that control their development. We studied LSCs in mouse models of acute myelogenous leukemia (AML) induced either by coexpression of the Hoxa9 and Meis1a oncogenes or by the fusion oncoprotein MLL-AF9. We show that the Wnt/β-catenin signaling pathway is required for self-renewal of LSCs that are derived from either hematopoietic stem cells (HSC) or more differentiated granulocyte-macrophage progenitors (GMP). Because the Wnt/β-catenin pathway is normally active in HSCs but not in GMP, these results suggest that reactivation of β-catenin signaling is required for the transformation of progenitor cells by certain oncogenes. β-catenin is not absolutely required for self-renewal of adult HSCs; thus, targeting the Wnt/β-catenin pathway may represent a new therapeutic opportunity in AML.</abstract><cop>Washington, DC</cop><pub>American Association for the Advancement of Science</pub><pmid>20339075</pmid><doi>10.1126/science.1186624</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0036-8075 |
| ispartof | Science (American Association for the Advancement of Science), 2010-03, Vol.327 (5973), p.1650-1653 |
| issn | 0036-8075 1095-9203 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3084586 |
| source | MEDLINE; JSTOR Archive Collection A-Z Listing; American Association for the Advancement of Science |
| subjects | Animals beta Catenin - metabolism Biological and medical sciences Cell Proliferation Cell Transformation, Neoplastic Genes, Homeobox Granulocyte-Macrophage Progenitor Cells - metabolism Granulocyte-Macrophage Progenitor Cells - pathology Hematologic and hematopoietic diseases Hematopoietic Stem Cells - metabolism Hematopoietic Stem Cells - pathology Homeodomain Proteins - genetics Indomethacin - pharmacology Leukemia, Myeloid, Acute - metabolism Leukemia, Myeloid, Acute - pathology Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis Medical sciences Mice Mice, Inbred C57BL Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins - genetics Neoplastic Stem Cells - pathology Signal Transduction Transduction, Genetic Wnt Proteins - metabolism |
| title | Wnt/β-Catenin Pathway Is Required for the Development of Leukemia Stem Cells in AML |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T16%3A57%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Wnt/%CE%B2-Catenin%20Pathway%20Is%20Required%20for%20the%20Development%20of%20Leukemia%20Stem%20Cells%20in%20AML&rft.jtitle=Science%20(American%20Association%20for%20the%20Advancement%20of%20Science)&rft.au=Wang,%20Yingzi&rft.date=2010-03-26&rft.volume=327&rft.issue=5973&rft.spage=1650&rft.epage=1653&rft.pages=1650-1653&rft.issn=0036-8075&rft.eissn=1095-9203&rft.coden=SCIEAS&rft_id=info:doi/10.1126/science.1186624&rft_dat=%3Cpubmed_cross%3E20339075%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/20339075&rfr_iscdi=true |