Dysregulated gene expression networks in human acute myelogenous leukemia stem cells
We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of L...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2009-03, Vol.106 (9), p.3396-3401 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Majeti, Ravindra Becker, Michael W Tian, Qiang Lee, Tsung-Lu Michael Yan, Xiaowei Liu, Rui Chiang, Jung-Hsien Hood, Leroy Clarke, Michael F Weissman, Irving L |
| description | We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells. |
| doi_str_mv | 10.1073/pnas.0900089106 |
| format | Article |
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Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.0900089106</identifier><identifier>PMID: 19218430</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Biological Sciences ; Blood ; Bone marrow ; Comparative analysis ; Databases, Nucleic Acid ; Datasets ; Gene expression ; Gene Expression Profiling ; Gene expression regulation ; Gene Expression Regulation, Neoplastic - genetics ; Gene Regulatory Networks - genetics ; Genes ; Genomics ; Hematopoietic stem cells ; Hematopoietic Stem Cells - metabolism ; Humans ; Kinases ; Leukemia ; Leukemia, Myeloid, Acute - genetics ; Myeloid leukemia ; Neoplastic Stem Cells - metabolism ; P values ; Signal transduction ; Stem cells</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2009-03, Vol.106 (9), p.3396-3401</ispartof><rights>Copyright National Academy of Sciences Mar 3, 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c616t-d3a7bf9ee12b38e042643829489d5ec9e279caa5b0d083a73ef8b1a6f7702a183</citedby><cites>FETCH-LOGICAL-c616t-d3a7bf9ee12b38e042643829489d5ec9e279caa5b0d083a73ef8b1a6f7702a183</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/106/9.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/40443326$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/40443326$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19218430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Majeti, Ravindra</creatorcontrib><creatorcontrib>Becker, Michael W</creatorcontrib><creatorcontrib>Tian, Qiang</creatorcontrib><creatorcontrib>Lee, Tsung-Lu Michael</creatorcontrib><creatorcontrib>Yan, Xiaowei</creatorcontrib><creatorcontrib>Liu, Rui</creatorcontrib><creatorcontrib>Chiang, Jung-Hsien</creatorcontrib><creatorcontrib>Hood, Leroy</creatorcontrib><creatorcontrib>Clarke, Michael F</creatorcontrib><creatorcontrib>Weissman, Irving L</creatorcontrib><title>Dysregulated gene expression networks in human acute myelogenous leukemia stem cells</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.</description><subject>Biological Sciences</subject><subject>Blood</subject><subject>Bone marrow</subject><subject>Comparative analysis</subject><subject>Databases, Nucleic Acid</subject><subject>Datasets</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene expression regulation</subject><subject>Gene Expression Regulation, Neoplastic - genetics</subject><subject>Gene Regulatory Networks - genetics</subject><subject>Genes</subject><subject>Genomics</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Humans</subject><subject>Kinases</subject><subject>Leukemia</subject><subject>Leukemia, Myeloid, Acute - genetics</subject><subject>Myeloid leukemia</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>P values</subject><subject>Signal transduction</subject><subject>Stem cells</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1DAURi0EokNhzQqwuoBV2uvHOPYGCZWnVIkF7dpykptppok92Ant_HsczahTWMDKi3vusT9_hLxkcMqgFGcb79IpGADQhoF6RBYMDCuUNPCYLAB4WWjJ5RF5ltI6U2ap4Sk5YoYzLQUsyOXHbYq4mno3YkNX6JHi3SZiSl3w1ON4G-JNop2n19PgPHX1NCIdttiHDIcp0R6nGxw6R9OIA62x79Nz8qR1fcIX-_OYXH3-dHn-tbj4_uXb-YeLolZMjUUjXFm1BpHxSmgEyZUUmhupTbPE2iAvTe3csoIGdGYFtrpiTrVlCdwxLY7J-513M1UDNjX6MbrebmI3uLi1wXX2z4nvru0q_LL5Iq6WJgve7gUx_JwwjXbo0hzBeczZrFJGG1WK_4IcOONLrTJ48he4DlP0-Rcyw4QQzMy2sx1Ux5Dy97f3T2Zg517t3Ks99Jo3Xj9MeuD3RT4A5s2DTlljhTCz4d0_AdtOfT_i3ZjJVztyncYQ71EJUgrBZ9Ob3bx1wbpV7JK9-jGHA6aAi9KI3zs0yoc</recordid><startdate>20090303</startdate><enddate>20090303</enddate><creator>Majeti, Ravindra</creator><creator>Becker, Michael W</creator><creator>Tian, Qiang</creator><creator>Lee, Tsung-Lu Michael</creator><creator>Yan, Xiaowei</creator><creator>Liu, Rui</creator><creator>Chiang, Jung-Hsien</creator><creator>Hood, Leroy</creator><creator>Clarke, Michael F</creator><creator>Weissman, Irving L</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7QO</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090303</creationdate><title>Dysregulated gene expression networks in human acute myelogenous leukemia stem cells</title><author>Majeti, Ravindra ; Becker, Michael W ; Tian, Qiang ; Lee, Tsung-Lu Michael ; Yan, Xiaowei ; Liu, Rui ; Chiang, Jung-Hsien ; Hood, Leroy ; Clarke, Michael F ; Weissman, Irving L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c616t-d3a7bf9ee12b38e042643829489d5ec9e279caa5b0d083a73ef8b1a6f7702a183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Biological Sciences</topic><topic>Blood</topic><topic>Bone marrow</topic><topic>Comparative analysis</topic><topic>Databases, Nucleic Acid</topic><topic>Datasets</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene expression regulation</topic><topic>Gene Expression Regulation, Neoplastic - genetics</topic><topic>Gene Regulatory Networks - genetics</topic><topic>Genes</topic><topic>Genomics</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Humans</topic><topic>Kinases</topic><topic>Leukemia</topic><topic>Leukemia, Myeloid, Acute - genetics</topic><topic>Myeloid leukemia</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>P values</topic><topic>Signal transduction</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Majeti, Ravindra</creatorcontrib><creatorcontrib>Becker, Michael W</creatorcontrib><creatorcontrib>Tian, Qiang</creatorcontrib><creatorcontrib>Lee, Tsung-Lu Michael</creatorcontrib><creatorcontrib>Yan, Xiaowei</creatorcontrib><creatorcontrib>Liu, Rui</creatorcontrib><creatorcontrib>Chiang, Jung-Hsien</creatorcontrib><creatorcontrib>Hood, Leroy</creatorcontrib><creatorcontrib>Clarke, Michael F</creatorcontrib><creatorcontrib>Weissman, Irving L</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Majeti, Ravindra</au><au>Becker, Michael W</au><au>Tian, Qiang</au><au>Lee, Tsung-Lu Michael</au><au>Yan, Xiaowei</au><au>Liu, Rui</au><au>Chiang, Jung-Hsien</au><au>Hood, Leroy</au><au>Clarke, Michael F</au><au>Weissman, Irving L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dysregulated gene expression networks in human acute myelogenous leukemia stem cells</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2009-03-03</date><risdate>2009</risdate><volume>106</volume><issue>9</issue><spage>3396</spage><epage>3401</epage><pages>3396-3401</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>We performed the first genome-wide expression analysis directly comparing the expression profile of highly enriched normal human hematopoietic stem cells (HSC) and leukemic stem cells (LSC) from patients with acute myeloid leukemia (AML). Comparing the expression signature of normal HSC to that of LSC, we identified 3,005 differentially expressed genes. Using 2 independent analyses, we identified multiple pathways that are aberrantly regulated in leukemic stem cells compared with normal HSC. Several pathways, including Wnt signaling, MAP Kinase signaling, and Adherens Junction, are well known for their role in cancer development and stem cell biology. Other pathways have not been previously implicated in the regulation of cancer stem cell functions, including Ribosome and T Cell Receptor Signaling pathway. This study demonstrates that combining global gene expression analysis with detailed annotated pathway resources applied to highly enriched normal and malignant stem cell populations, can yield an understanding of the critical pathways regulating cancer stem cells.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>19218430</pmid><doi>10.1073/pnas.0900089106</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2009-03, Vol.106 (9), p.3396-3401 |
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| subjects | Biological Sciences Blood Bone marrow Comparative analysis Databases, Nucleic Acid Datasets Gene expression Gene Expression Profiling Gene expression regulation Gene Expression Regulation, Neoplastic - genetics Gene Regulatory Networks - genetics Genes Genomics Hematopoietic stem cells Hematopoietic Stem Cells - metabolism Humans Kinases Leukemia Leukemia, Myeloid, Acute - genetics Myeloid leukemia Neoplastic Stem Cells - metabolism P values Signal transduction Stem cells |
| title | Dysregulated gene expression networks in human acute myelogenous leukemia stem cells |
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