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Instead, Pten deficiency causes an up-regulation of the PI3K pathway in myeloid cells, but not in HSCs. Strikingly, myeloid cells secrete high levels of G-CSF upon Pten loss, leading to the mobilization of HSCs from the bone marrow and accumulation in the spleen. After deletion of Pten in mice lacking G-CSF, the splenomegaly, myeloproliferative disease, and splenic HSC accumulation are rescued. Our data show that although PTEN has little if any role in normal HSCs, it is essential to prevent overt G-CSF production by myeloid and stromal cells which otherwise causes HSCs to relocate to the spleen followed by lethal leukemia initiation.<\/jats:p>","DOI":"10.1084\/jem.20122768","type":"journal-article","created":{"date-parts":[[2013,10,15]],"date-time":"2013-10-15T00:51:08Z","timestamp":1381798268000},"page":"2337-2349","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Pten loss in the bone marrow leads to G-CSF\u2013mediated HSC mobilization"],"prefix":"10.1084","volume":"210","author":[{"given":"Melania","family":"Tesio","sequence":"first","affiliation":[{"name":"Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany 1"},{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), D-69120 Heidelberg, Germany 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriela M.","family":"Oser","sequence":"additional","affiliation":[{"name":"Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany 1"},{"name":"Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ir\u00e8ne","family":"Baccelli","sequence":"additional","affiliation":[{"name":"Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany 1"},{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), D-69120 Heidelberg, Germany 2"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Blanco-Bose","sequence":"additional","affiliation":[{"name":"Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland 3"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Medical Pharmacology, Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 4"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim R.","family":"G\u00f6thert","sequence":"additional","affiliation":[{"name":"Department of Hematology, Universit\u00e4tsklinikum Essen, Westdeutsches Tumorzentrum (WTZ), D- 45147 Essen, Germany 5"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Kogan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143 6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Trumpp","sequence":"additional","affiliation":[{"name":"Deutsches Krebsforschungszentrum (DKFZ), D-69120 Heidelberg, Germany 1"},{"name":"Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGMBH), D-69120 Heidelberg, Germany 2"},{"name":"Swiss Institute for Experimental Cancer Research (ISREC), School of Life Science, Ecole Polytechnique F\u00e9d\u00e9rale de Lausanne (EPFL), 1015 Lausanne, Switzerland 3"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2013,10,14]]},"reference":[{"key":"2023072601152482900_bib1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.cell.2004.07.004","article-title":"Tie2\/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche","volume":"118","author":"Arai","year":"2004","journal-title":"Cell."},{"key":"2023072601152482900_bib2","doi-asserted-by":"crossref","first-page":"5904","DOI":"10.4049\/jimmunol.181.9.5904","article-title":"A quantitative trait locus on chromosome 4 affects cycling of hematopoietic stem and progenitor cells through regulation of TGF-beta 2 responsiveness","volume":"181","author":"Avagyan","year":"2008","journal-title":"J. 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