PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention
Cancer stem cell function Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death....
Gespeichert in:
| Veröffentlicht in: | Nature 2006-05, Vol.441 (7092), p.518-522 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 522 |
|---|---|
| container_issue | 7092 |
| container_start_page | 518 |
| container_title | Nature |
| container_volume | 441 |
| creator | Zhang, Jiwang Grindley, Justin C. Yin, Tong Jayasinghe, Sachintha He, Xi C. Ross, Jason T. Haug, Jeffrey S. Rupp, Dawn Porter-Westpfahl, Kimberly S. Wiedemann, Leanne M. Wu, Hong Li, Linheng |
| description | Cancer stem cell function
Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death. Now a study of the tumour suppressor PTEN, often inactivated in leukaemia and other cancers, pinpoints a major difference between self-renewal in normal and cancer stem cells. PTEN normally inhibits the phosphatidylinositol-3-OH kinase signalling pathway, limiting cell proliferation and survival. In the absence of PTEN, leukaemic stem cells proliferate, but normal stem cells are depleted. This suggests that PTEN-mimicking drugs may act against leukaemia yet preserve blood stem cells. Indeed, in Pten-deficient mice rapamycin kills leukaemic stem cells but rescues normal stem cell function. A separate study confirms PTEN's role in blood stem cell regulation.
Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance
1
,
2
,
3
. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)–Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration
4
,
5
. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD)
6
. Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis. |
| doi_str_mv | 10.1038/nature04747 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_68012501</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A632098712</galeid><sourcerecordid>A632098712</sourcerecordid><originalsourceid>FETCH-LOGICAL-c707t-706ff108a01f13ee1c320d259f6af78eba1a0881185f760d9c02acd724ca3f93</originalsourceid><addsrcrecordid>eNqF092L1DAQAPAiineuPvku5URBtGc-2iR9XJZTD45TdMEXocxlJ3s523QvSUX_e7O3C3srlaWUQvLLZJjpZNlzSk4p4eq9gzh4JKUs5YPsmJZSFKVQ8mF2TAhTBVFcHGVPQrghhFRUlo-zIyoE57wkx9mPL_Ozy7wD62J6Q34N2EHsV73FaHUeIna5xrYNObhFDjqG3Lq8tQ5hibm-7q3Gu60Wh5_prIV85fEXumh79zR7ZKAN-Gz7nWTzD2fz2afi4vPH89n0otCSyFhIIoyhRAGhhnJEqjkjC1bVRoCRCq-AAlGKUlUZKcii1oSBXkhWauCm5pPs9Sbsyve3A4bYdDaskwaH_RAaoQhlFaEHIRdU1kxWByFTRArBDkdklEpeicM50rquJWciwZN_4E0_eJfK1zBSVrymqXWT7OUGLaHFxjrTRw96HbGZilS8WknKkipG1BIdemh7h8am5T1_MuL1yt4299HpCErPIjVfj0Z9s3cgmYi_4xKGEJrzb1_37dv_2-n8--xyVGvfh-DRNCtvO_B_Gkqa9Wg090Yj6Rfbwg5XHS52djsLCbzaAggaWuPBaRt2Tkqp2N1f9G7jQtpyS_S7Do3d-xcNVB-p</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>204539163</pqid></control><display><type>article</type><title>PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><source>Nature Journals Online</source><creator>Zhang, Jiwang ; Grindley, Justin C. ; Yin, Tong ; Jayasinghe, Sachintha ; He, Xi C. ; Ross, Jason T. ; Haug, Jeffrey S. ; Rupp, Dawn ; Porter-Westpfahl, Kimberly S. ; Wiedemann, Leanne M. ; Wu, Hong ; Li, Linheng</creator><creatorcontrib>Zhang, Jiwang ; Grindley, Justin C. ; Yin, Tong ; Jayasinghe, Sachintha ; He, Xi C. ; Ross, Jason T. ; Haug, Jeffrey S. ; Rupp, Dawn ; Porter-Westpfahl, Kimberly S. ; Wiedemann, Leanne M. ; Wu, Hong ; Li, Linheng</creatorcontrib><description>Cancer stem cell function
Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death. Now a study of the tumour suppressor PTEN, often inactivated in leukaemia and other cancers, pinpoints a major difference between self-renewal in normal and cancer stem cells. PTEN normally inhibits the phosphatidylinositol-3-OH kinase signalling pathway, limiting cell proliferation and survival. In the absence of PTEN, leukaemic stem cells proliferate, but normal stem cells are depleted. This suggests that PTEN-mimicking drugs may act against leukaemia yet preserve blood stem cells. Indeed, in Pten-deficient mice rapamycin kills leukaemic stem cells but rescues normal stem cell function. A separate study confirms PTEN's role in blood stem cell regulation.
Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance
1
,
2
,
3
. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)–Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration
4
,
5
. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD)
6
. Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>EISSN: 1476-4679</identifier><identifier>DOI: 10.1038/nature04747</identifier><identifier>PMID: 16633340</identifier><identifier>CODEN: NATUAS</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>Activation ; AKT protein ; Animal tumors. Experimental tumors ; Animals ; Biological and medical sciences ; Bone marrow ; Cell Count ; Cell Cycle ; Cell Lineage ; Cell Proliferation ; Cell survival ; Cyclin D1 - metabolism ; Deactivation ; Experimental malignant blood diseases ; Gene Expression ; Health aspects ; Hematopoietic stem cells ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - metabolism ; Homology ; Humanities and Social Sciences ; Inactivation ; letter ; Leukemia ; Leukemia - metabolism ; Leukemia - pathology ; Leukemia - prevention & control ; Medical sciences ; Mice ; Molecular biology ; multidisciplinary ; Mutation ; Mutation - genetics ; Myeloproliferative diseases ; Oncology ; Prevention ; PTEN Phosphohydrolase - deficiency ; PTEN Phosphohydrolase - genetics ; PTEN Phosphohydrolase - metabolism ; PTEN protein ; Rodents ; Science ; Science (multidisciplinary) ; Stem cell transplantation ; Stem cells ; Tensin ; Tumors</subject><ispartof>Nature, 2006-05, Vol.441 (7092), p.518-522</ispartof><rights>Springer Nature Limited 2006</rights><rights>2006 INIST-CNRS</rights><rights>COPYRIGHT 2006 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group May 25, 2006</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c707t-706ff108a01f13ee1c320d259f6af78eba1a0881185f760d9c02acd724ca3f93</citedby><cites>FETCH-LOGICAL-c707t-706ff108a01f13ee1c320d259f6af78eba1a0881185f760d9c02acd724ca3f93</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nature04747$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nature04747$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=17778201$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16633340$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Jiwang</creatorcontrib><creatorcontrib>Grindley, Justin C.</creatorcontrib><creatorcontrib>Yin, Tong</creatorcontrib><creatorcontrib>Jayasinghe, Sachintha</creatorcontrib><creatorcontrib>He, Xi C.</creatorcontrib><creatorcontrib>Ross, Jason T.</creatorcontrib><creatorcontrib>Haug, Jeffrey S.</creatorcontrib><creatorcontrib>Rupp, Dawn</creatorcontrib><creatorcontrib>Porter-Westpfahl, Kimberly S.</creatorcontrib><creatorcontrib>Wiedemann, Leanne M.</creatorcontrib><creatorcontrib>Wu, Hong</creatorcontrib><creatorcontrib>Li, Linheng</creatorcontrib><title>PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention</title><title>Nature</title><addtitle>Nature</addtitle><addtitle>Nature</addtitle><description>Cancer stem cell function
Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death. Now a study of the tumour suppressor PTEN, often inactivated in leukaemia and other cancers, pinpoints a major difference between self-renewal in normal and cancer stem cells. PTEN normally inhibits the phosphatidylinositol-3-OH kinase signalling pathway, limiting cell proliferation and survival. In the absence of PTEN, leukaemic stem cells proliferate, but normal stem cells are depleted. This suggests that PTEN-mimicking drugs may act against leukaemia yet preserve blood stem cells. Indeed, in Pten-deficient mice rapamycin kills leukaemic stem cells but rescues normal stem cell function. A separate study confirms PTEN's role in blood stem cell regulation.
Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance
1
,
2
,
3
. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)–Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration
4
,
5
. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD)
6
. Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.</description><subject>Activation</subject><subject>AKT protein</subject><subject>Animal tumors. Experimental tumors</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Bone marrow</subject><subject>Cell Count</subject><subject>Cell Cycle</subject><subject>Cell Lineage</subject><subject>Cell Proliferation</subject><subject>Cell survival</subject><subject>Cyclin D1 - metabolism</subject><subject>Deactivation</subject><subject>Experimental malignant blood diseases</subject><subject>Gene Expression</subject><subject>Health aspects</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Homology</subject><subject>Humanities and Social Sciences</subject><subject>Inactivation</subject><subject>letter</subject><subject>Leukemia</subject><subject>Leukemia - metabolism</subject><subject>Leukemia - pathology</subject><subject>Leukemia - prevention & control</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Molecular biology</subject><subject>multidisciplinary</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Myeloproliferative diseases</subject><subject>Oncology</subject><subject>Prevention</subject><subject>PTEN Phosphohydrolase - deficiency</subject><subject>PTEN Phosphohydrolase - genetics</subject><subject>PTEN Phosphohydrolase - metabolism</subject><subject>PTEN protein</subject><subject>Rodents</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Stem cell transplantation</subject><subject>Stem cells</subject><subject>Tensin</subject><subject>Tumors</subject><issn>0028-0836</issn><issn>1476-4687</issn><issn>1476-4679</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqF092L1DAQAPAiineuPvku5URBtGc-2iR9XJZTD45TdMEXocxlJ3s523QvSUX_e7O3C3srlaWUQvLLZJjpZNlzSk4p4eq9gzh4JKUs5YPsmJZSFKVQ8mF2TAhTBVFcHGVPQrghhFRUlo-zIyoE57wkx9mPL_Ozy7wD62J6Q34N2EHsV73FaHUeIna5xrYNObhFDjqG3Lq8tQ5hibm-7q3Gu60Wh5_prIV85fEXumh79zR7ZKAN-Gz7nWTzD2fz2afi4vPH89n0otCSyFhIIoyhRAGhhnJEqjkjC1bVRoCRCq-AAlGKUlUZKcii1oSBXkhWauCm5pPs9Sbsyve3A4bYdDaskwaH_RAaoQhlFaEHIRdU1kxWByFTRArBDkdklEpeicM50rquJWciwZN_4E0_eJfK1zBSVrymqXWT7OUGLaHFxjrTRw96HbGZilS8WknKkipG1BIdemh7h8am5T1_MuL1yt4299HpCErPIjVfj0Z9s3cgmYi_4xKGEJrzb1_37dv_2-n8--xyVGvfh-DRNCtvO_B_Gkqa9Wg090Yj6Rfbwg5XHS52djsLCbzaAggaWuPBaRt2Tkqp2N1f9G7jQtpyS_S7Do3d-xcNVB-p</recordid><startdate>20060525</startdate><enddate>20060525</enddate><creator>Zhang, Jiwang</creator><creator>Grindley, Justin C.</creator><creator>Yin, Tong</creator><creator>Jayasinghe, Sachintha</creator><creator>He, Xi C.</creator><creator>Ross, Jason T.</creator><creator>Haug, Jeffrey S.</creator><creator>Rupp, Dawn</creator><creator>Porter-Westpfahl, Kimberly S.</creator><creator>Wiedemann, Leanne M.</creator><creator>Wu, Hong</creator><creator>Li, Linheng</creator><general>Nature Publishing Group UK</general><general>Nature Publishing</general><general>Nature Publishing Group</general><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>ATWCN</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7ST</scope><scope>7T5</scope><scope>7TG</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88G</scope><scope>88I</scope><scope>8AF</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>BKSAR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>M2O</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PCBAR</scope><scope>PDBOC</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PSYQQ</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>R05</scope><scope>RC3</scope><scope>S0X</scope><scope>SOI</scope><scope>7QO</scope><scope>7U5</scope><scope>L7M</scope><scope>7SC</scope><scope>7SP</scope><scope>7SR</scope><scope>7TB</scope><scope>8BQ</scope><scope>F28</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L~C</scope><scope>L~D</scope><scope>7X8</scope></search><sort><creationdate>20060525</creationdate><title>PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention</title><author>Zhang, Jiwang ; Grindley, Justin C. ; Yin, Tong ; Jayasinghe, Sachintha ; He, Xi C. ; Ross, Jason T. ; Haug, Jeffrey S. ; Rupp, Dawn ; Porter-Westpfahl, Kimberly S. ; Wiedemann, Leanne M. ; Wu, Hong ; Li, Linheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c707t-706ff108a01f13ee1c320d259f6af78eba1a0881185f760d9c02acd724ca3f93</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Activation</topic><topic>AKT protein</topic><topic>Animal tumors. Experimental tumors</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Bone marrow</topic><topic>Cell Count</topic><topic>Cell Cycle</topic><topic>Cell Lineage</topic><topic>Cell Proliferation</topic><topic>Cell survival</topic><topic>Cyclin D1 - metabolism</topic><topic>Deactivation</topic><topic>Experimental malignant blood diseases</topic><topic>Gene Expression</topic><topic>Health aspects</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Homology</topic><topic>Humanities and Social Sciences</topic><topic>Inactivation</topic><topic>letter</topic><topic>Leukemia</topic><topic>Leukemia - metabolism</topic><topic>Leukemia - pathology</topic><topic>Leukemia - prevention & control</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Molecular biology</topic><topic>multidisciplinary</topic><topic>Mutation</topic><topic>Mutation - genetics</topic><topic>Myeloproliferative diseases</topic><topic>Oncology</topic><topic>Prevention</topic><topic>PTEN Phosphohydrolase - deficiency</topic><topic>PTEN Phosphohydrolase - genetics</topic><topic>PTEN Phosphohydrolase - metabolism</topic><topic>PTEN protein</topic><topic>Rodents</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tensin</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Jiwang</creatorcontrib><creatorcontrib>Grindley, Justin C.</creatorcontrib><creatorcontrib>Yin, Tong</creatorcontrib><creatorcontrib>Jayasinghe, Sachintha</creatorcontrib><creatorcontrib>He, Xi C.</creatorcontrib><creatorcontrib>Ross, Jason T.</creatorcontrib><creatorcontrib>Haug, Jeffrey S.</creatorcontrib><creatorcontrib>Rupp, Dawn</creatorcontrib><creatorcontrib>Porter-Westpfahl, Kimberly S.</creatorcontrib><creatorcontrib>Wiedemann, Leanne M.</creatorcontrib><creatorcontrib>Wu, Hong</creatorcontrib><creatorcontrib>Li, Linheng</creatorcontrib><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>Gale In Context: Middle School</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Environment Abstracts</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical 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>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Psychology Database (Alumni)</collection><collection>Science Database (Alumni Edition)</collection><collection>STEM Database</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology 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>Research Library (Alumni Edition)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Earth, Atmospheric & Aquatic Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</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>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Psychology</collection><collection>Research Library</collection><collection>Science Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Earth, Atmospheric & Aquatic Science Database</collection><collection>Materials Science Collection</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 One Psychology</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>University of Michigan</collection><collection>Genetics Abstracts</collection><collection>SIRS Editorial</collection><collection>Environment Abstracts</collection><collection>Biotechnology Research Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>Computer and Information Systems Abstracts</collection><collection>Electronics & Communications Abstracts</collection><collection>Engineered Materials Abstracts</collection><collection>Mechanical & Transportation Engineering Abstracts</collection><collection>METADEX</collection><collection>ANTE: Abstracts in New Technology & Engineering</collection><collection>Materials Research Database</collection><collection>ProQuest Computer Science Collection</collection><collection>Civil Engineering Abstracts</collection><collection>Computer and Information Systems Abstracts Academic</collection><collection>Computer and Information Systems Abstracts Professional</collection><collection>MEDLINE - Academic</collection><jtitle>Nature</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Jiwang</au><au>Grindley, Justin C.</au><au>Yin, Tong</au><au>Jayasinghe, Sachintha</au><au>He, Xi C.</au><au>Ross, Jason T.</au><au>Haug, Jeffrey S.</au><au>Rupp, Dawn</au><au>Porter-Westpfahl, Kimberly S.</au><au>Wiedemann, Leanne M.</au><au>Wu, Hong</au><au>Li, Linheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention</atitle><jtitle>Nature</jtitle><stitle>Nature</stitle><addtitle>Nature</addtitle><date>2006-05-25</date><risdate>2006</risdate><volume>441</volume><issue>7092</issue><spage>518</spage><epage>522</epage><pages>518-522</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><eissn>1476-4679</eissn><coden>NATUAS</coden><abstract>Cancer stem cell function
Stem cells that initiate and maintain cancers are so like normal stem cells that it's hard to design drugs to target them specifically. This is a serious problem as, for example, damaging blood stem cells in leukaemia therapy can cause haematopoietic failure and death. Now a study of the tumour suppressor PTEN, often inactivated in leukaemia and other cancers, pinpoints a major difference between self-renewal in normal and cancer stem cells. PTEN normally inhibits the phosphatidylinositol-3-OH kinase signalling pathway, limiting cell proliferation and survival. In the absence of PTEN, leukaemic stem cells proliferate, but normal stem cells are depleted. This suggests that PTEN-mimicking drugs may act against leukaemia yet preserve blood stem cells. Indeed, in Pten-deficient mice rapamycin kills leukaemic stem cells but rescues normal stem cell function. A separate study confirms PTEN's role in blood stem cell regulation.
Haematopoietic stem cells (HSCs) must achieve a balance between quiescence and activation that fulfils immediate demands for haematopoiesis without compromising long-term stem cell maintenance, yet little is known about the molecular events governing this balance
1
,
2
,
3
. Phosphatase and tensin homologue (PTEN) functions as a negative regulator of the phosphatidylinositol-3-OH kinase (PI(3)K)–Akt pathway, which has crucial roles in cell proliferation, survival, differentiation and migration
4
,
5
. Here we show that inactivation of PTEN in bone marrow HSCs causes their short-term expansion, but long-term decline, primarily owing to an enhanced level of HSC activation. PTEN-deficient HSCs engraft normally in recipient mice, but have an impaired ability to sustain haematopoietic reconstitution, reflecting the dysregulation of their cell cycle and decreased retention in the bone marrow niche. Mice with PTEN-mutant bone marrow also have an increased representation of myeloid and T-lymphoid lineages and develop myeloproliferative disorder (MPD)
6
. Notably, the cell populations that expand in PTEN mutants match those that become dominant in the acute myeloid/lymphoid leukaemia that develops in the later stages of MPD. Thus, PTEN has essential roles in restricting the activation of HSCs, in lineage fate determination, and in the prevention of leukaemogenesis.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>16633340</pmid><doi>10.1038/nature04747</doi><tpages>5</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature, 2006-05, Vol.441 (7092), p.518-522 |
| issn | 0028-0836 1476-4687 1476-4679 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_68012501 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Activation AKT protein Animal tumors. Experimental tumors Animals Biological and medical sciences Bone marrow Cell Count Cell Cycle Cell Lineage Cell Proliferation Cell survival Cyclin D1 - metabolism Deactivation Experimental malignant blood diseases Gene Expression Health aspects Hematopoietic stem cells Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - metabolism Homology Humanities and Social Sciences Inactivation letter Leukemia Leukemia - metabolism Leukemia - pathology Leukemia - prevention & control Medical sciences Mice Molecular biology multidisciplinary Mutation Mutation - genetics Myeloproliferative diseases Oncology Prevention PTEN Phosphohydrolase - deficiency PTEN Phosphohydrolase - genetics PTEN Phosphohydrolase - metabolism PTEN protein Rodents Science Science (multidisciplinary) Stem cell transplantation Stem cells Tensin Tumors |
| title | PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-27T07%3A47%3A26IST&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=PTEN%20maintains%20haematopoietic%20stem%20cells%20and%20acts%20in%20lineage%20choice%20and%20leukaemia%20prevention&rft.jtitle=Nature&rft.au=Zhang,%20Jiwang&rft.date=2006-05-25&rft.volume=441&rft.issue=7092&rft.spage=518&rft.epage=522&rft.pages=518-522&rft.issn=0028-0836&rft.eissn=1476-4687&rft.coden=NATUAS&rft_id=info:doi/10.1038/nature04747&rft_dat=%3Cgale_proqu%3EA632098712%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=204539163&rft_id=info:pmid/16633340&rft_galeid=A632098712&rfr_iscdi=true |