{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T17:32:29Z","timestamp":1791307949122,"version":"4.3.1"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"7569","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2015,9]]},"DOI":"10.1038\/nature15248","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T13:57:41Z","timestamp":1441202261000},"page":"380-383","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":269,"title":["Erosion of the chronic myeloid leukaemia stem cell pool by PPAR\u03b3 agonists"],"prefix":"10.1038","volume":"525","author":[{"given":"St\u00e9phane","family":"Prost","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis","family":"Relouzat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Spentchian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine","family":"Ouzegdouh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G\u00e9rald","family":"Massonnet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Paul","family":"Beressi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Els","family":"Verhoeyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Raggueneau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Maneglier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Castaigne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Chomienne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stany","family":"Chr\u00e9tien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Rousselot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Leboulch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,9,2]]},"reference":[{"key":"BFnature15248_CR1","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1038\/nrc3184","volume":"12","author":"LV Nguyen","year":"2012","unstructured":"Nguyen, L. V., Vanner, R., Dirks, P. & Eaves, C. J. Cancer stem cells: an evolving concept. Nature Rev. Cancer 12, 133\u2013143 (2012)","journal-title":"Nature Rev. Cancer"},{"key":"BFnature15248_CR2","doi-asserted-by":"publisher","first-page":"713","DOI":"10.18632\/oncotarget.333","volume":"2","author":"JC Chomel","year":"2011","unstructured":"Chomel, J. C. & Turhan, A. G. Chronic myeloid leukemia stem cells in the era of targeted therapies: resistance, persistence and long-term dormancy. Oncotarget 2, 713\u2013727 (2011)","journal-title":"Oncotarget"},{"key":"BFnature15248_CR3","doi-asserted-by":"publisher","first-page":"3358","DOI":"10.1200\/JCO.2007.15.8154","volume":"26","author":"H de Lavallade","year":"2008","unstructured":"de Lavallade, H. et al. Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis. J. Clin. Oncol. 26, 3358\u20133363 (2008)","journal-title":"J. Clin. Oncol."},{"key":"BFnature15248_CR4","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1172\/JCI35721","volume":"121","author":"AS Corbin","year":"2011","unstructured":"Corbin, A. S. et al. Human chronic myeloid leukemia stem cells are insensitive to imatinib despite inhibition of BCR-ABL activity. J. Clin. Invest. 121, 396\u2013409 (2011)","journal-title":"J. Clin. Invest."},{"key":"BFnature15248_CR5","doi-asserted-by":"publisher","first-page":"4528","DOI":"10.1091\/mbc.e06-05-0419","volume":"18","author":"CJ Hu","year":"2007","unstructured":"Hu, C. J., Sataur, A., Wang, L., Chen, H. & Simon, M. C. The N-terminal transactivation domain confers target gene specificity of hypoxia-inducible factors HIF-1\u03b1 and HIF-2\u03b1. Mol. Biol. Cell 18, 4528\u20134542 (2007)","journal-title":"Mol. Biol. Cell"},{"key":"BFnature15248_CR6","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1097\/MOH.0b013e3283606022","volume":"20","author":"J Du","year":"2013","unstructured":"Du, J. & Yang, Y. C. Cited2 in hematopoietic stem cell function. Curr. Opin. Hematol. 20, 301\u2013307 (2013)","journal-title":"Curr. Opin. Hematol."},{"key":"BFnature15248_CR7","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1182\/blood.V99.1.319","volume":"99","author":"SM Graham","year":"2002","unstructured":"Graham, S. M. et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 99, 319\u2013325 (2002)","journal-title":"Blood"},{"key":"BFnature15248_CR8","doi-asserted-by":"publisher","first-page":"4016","DOI":"10.1182\/blood-2006-11-057521","volume":"109","author":"HG J\u00f8rgensen","year":"2007","unstructured":"J\u00f8rgensen, H. G., Allan, E. K., Jordanides, N. E., Mountford, J. C. & Holyoake, T. L. Nilotinib exerts equipotent antiproliferative effects to imatinib and does not induce apoptosis in CD34+ CML cells. Blood 109, 4016\u20134019 (2007)","journal-title":"Blood"},{"key":"BFnature15248_CR9","doi-asserted-by":"publisher","first-page":"4532","DOI":"10.1182\/blood-2005-07-2947","volume":"107","author":"M Copland","year":"2006","unstructured":"Copland, M. et al. Dasatinib (BMS-354825) targets an earlier progenitor population than imatinib in primary CML but does not eliminate the quiescent fraction. Blood 107, 4532\u20134539 (2006)","journal-title":"Blood"},{"key":"BFnature15248_CR10","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/j.cell.2009.02.024","volume":"136","author":"J Luo","year":"2009","unstructured":"Luo, J., Solimini, N. L. & Elledge, S. J. Principles of cancer therapy: oncogene and non-oncogene addiction. Cell 136, 823\u2013837 (2009)","journal-title":"Cell"},{"key":"BFnature15248_CR11","first-page":"1765","volume":"118","author":"S Prost","year":"2008","unstructured":"Prost, S. et al. Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef\/PPAR\u03b3\/STAT5 signaling pathway in macaques. J. Clin. Invest. 118, 1765\u20131775 (2008)","journal-title":"J. Clin. Invest."},{"key":"BFnature15248_CR12","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1038\/sj.clpt.6100146","volume":"82","author":"R Berria","year":"2007","unstructured":"Berria, R. et al. Reduction in hematocrit and hemoglobin following pioglitazone treatment is not hemodilutional in Type II diabetes mellitus. Clin. Pharmacol. Ther. 82, 275\u2013281 (2007)","journal-title":"Clin. Pharmacol. Ther."},{"key":"BFnature15248_CR13","doi-asserted-by":"publisher","first-page":"6078","DOI":"10.1182\/blood-2011-07-365080","volume":"118","author":"S Avagyan","year":"2011","unstructured":"Avagyan, S., Aguilo, F., Kamezaki, K. & Snoeck, H. W. Quantitative trait mapping reveals a regulatory axis involving peroxisome proliferator-activated receptors, PRDM16, transforming growth factor-\u03b22 and FLT3 in hematopoiesis. Blood 118, 6078\u20136086 (2011)","journal-title":"Blood"},{"key":"BFnature15248_CR14","doi-asserted-by":"publisher","first-page":"4856","DOI":"10.1182\/blood-2008-09-181107","volume":"113","author":"Z Wang","year":"2009","unstructured":"Wang, Z., Li, G., Tse, W. & Bunting, K. D. Conditional deletion of STAT5 in adult mouse hematopoietic stem cells causes loss of quiescence and permits efficient nonablative stem cell replacement. Blood 113, 4856\u20134865 (2009)","journal-title":"Blood"},{"key":"BFnature15248_CR15","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1002\/emmm.201000062","volume":"2","author":"A Hoelbl","year":"2010","unstructured":"Hoelbl, A. et al. Stat5 is indispensable for the maintenance of bcr\/abl-positive leukaemia. EMBO Mol. Med. 2, 98\u2013110 (2010)","journal-title":"EMBO Mol. Med."},{"key":"BFnature15248_CR16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1101\/gad.14.2.232","volume":"14","author":"M Kieslinger","year":"2000","unstructured":"Kieslinger, M. et al. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Genes Dev. 14, 232\u2013244 (2000)","journal-title":"Genes Dev."},{"key":"BFnature15248_CR17","doi-asserted-by":"publisher","first-page":"3320","DOI":"10.1182\/blood-2010-08-303669","volume":"117","author":"S Fatrai","year":"2011","unstructured":"Fatrai, S., Wierenga, A. T., Daenen, S. M., Vellenga, E. & Schuringa, J. J. Identification of HIF2\u03b1 as an important STAT5 target gene in human hematopoietic stem cells. Blood 117, 3320\u20133330 (2011)","journal-title":"Blood"},{"key":"BFnature15248_CR18","doi-asserted-by":"publisher","first-page":"3148","DOI":"10.1182\/blood.V89.9.3148","volume":"89","author":"A Matsumoto","year":"1997","unstructured":"Matsumoto, A. et al. CIS, a cytokine inducible SH2 protein, is a target of the JAK-STAT5 pathway and modulates STAT5 activation. Blood 89, 3148\u20133154 (1997)","journal-title":"Blood"},{"key":"BFnature15248_CR19","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1158\/1535-7163.MCT-13-0341","volume":"13","author":"S Liu","year":"2014","unstructured":"Liu, S. et al. Targeting STAT5 in hematologic malignancies through inhibition of the bromodomain and extra-terminal (BET) bromodomain protein BRD2. Mol. Cancer Ther. 13, 1194\u20131205 (2014)","journal-title":"Mol. Cancer Ther."},{"key":"BFnature15248_CR20","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/j.exphem.2012.05.013","volume":"40","author":"L Wang","year":"2012","unstructured":"Wang, L., Giannoudis, A., Austin, G. & Clark, R. E. Peroxisome proliferator-activated receptor activation increases imatinib uptake and killing of chronic myeloid leukemia cells. Exp. Hematol. 40, 811\u2013819 (2012)","journal-title":"Exp. Hematol."},{"key":"BFnature15248_CR21","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.1124\/mol.104.006445","volume":"67","author":"A Szanto","year":"2005","unstructured":"Szanto, A. & Nagy, L. Retinoids potentiate peroxisome proliferator-activated receptor gamma action in differentiation, gene expression, and lipid metabolic processes in developing myeloid cells. Mol. Pharmacol. 67, 1935\u20131943 (2005)","journal-title":"Mol. Pharmacol."},{"key":"BFnature15248_CR22","doi-asserted-by":"publisher","first-page":"2889","DOI":"10.1182\/blood-2007-01-066316","volume":"110","author":"Y Chen","year":"2007","unstructured":"Chen, Y., Haviernik, P., Bunting, K. D. & Yang, Y. C. Cited2 is required for normal hematopoiesis in the murine fetal liver. Blood 110, 2889\u20132898 (2007)","journal-title":"Blood"},{"key":"BFnature15248_CR23","doi-asserted-by":"publisher","first-page":"2789","DOI":"10.1182\/blood-2011-10-387902","volume":"119","author":"J Du","year":"2012","unstructured":"Du, J. et al. HIF-1\u03b1 deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency. Blood 119, 2789\u20132798 (2012)","journal-title":"Blood"},{"key":"BFnature15248_CR24","first-page":"65","volume":"1","author":"S Koschmieder","year":"2011","unstructured":"Koschmieder, S. & Schemionek, M. Mouse models as tools to understand and study BCR-ABL1 diseases. Am. J. Blood Res. 1, 65\u201375 (2011)","journal-title":"Am. J. Blood Res."},{"key":"BFnature15248_CR25","doi-asserted-by":"crossref","unstructured":"Rousselot, P. et al. Targeting STAT5 expression resulted in molecular response improvement in patients with chronic phase CML treated with imatinib. ASH Annual Meeting Abstracts (2012)","DOI":"10.1182\/blood.V120.21.696.696"},{"key":"BFnature15248_CR26","first-page":"79","volume":"3","author":"GF Davies","year":"2009","unstructured":"Davies, G. F., Juurlink, B. H. & Harkness, T. A. Troglitazone reverses the multiple drug resistance phenotype in cancer cells. Drug Des. Devel. Ther. 3, 79\u201388 (2009)","journal-title":"Drug Des. Devel. Ther."},{"key":"BFnature15248_CR27","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1182\/blood-2011-06-361691","volume":"119","author":"H Yuan","year":"2012","unstructured":"Yuan, H. et al. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis. Blood 119, 1904\u20131914 (2012)","journal-title":"Blood"},{"key":"BFnature15248_CR28","first-page":"2331","volume":"29","author":"N Pitulis","year":"2009","unstructured":"Pitulis, N., Papageorgiou, E., Tenta, R., Lembessis, P. & Koutsilieris, M. IL-6 and PPAR\u03b3 signalling in human PC-3 prostate cancer cells. Anticancer Res. 29, 2331\u20132337 (2009)","journal-title":"Anticancer Res."},{"key":"BFnature15248_CR29","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/ng.389","volume":"41","author":"Y Chen","year":"2009","unstructured":"Chen, Y., Hu, Y., Zhang, H., Peng, C. & Li, S. Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia. Nature Genet. 41, 783\u2013792 (2009)","journal-title":"Nature Genet."},{"key":"BFnature15248_CR30","doi-asserted-by":"publisher","first-page":"3442","DOI":"10.1158\/1078-0432.CCR-08-3291","volume":"15","author":"DJ Kominsky","year":"2009","unstructured":"Kominsky, D. J. et al. Abnormalities in glucose uptake and metabolism in imatinib-resistant human BCR-ABL-positive cells. Clin. Canc. Res. 15, 3442\u20133450 (2009)","journal-title":"Clin. Canc. Res."},{"key":"BFnature15248_CR31","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.ejphar.2010.03.010","volume":"636","author":"D Lu","year":"2010","unstructured":"Lu, D. & Carson, D. A. Repression of beta-catenin signaling by PPAR gamma ligands. Eur. J. Pharmacol. 636, 198\u2013202 (2010)","journal-title":"Eur. J. Pharmacol."},{"key":"BFnature15248_CR32","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1038\/nm.2882","volume":"18","author":"K Ito","year":"2012","unstructured":"Ito, K. et al. A PML\u2013PPAR-\u03b4 pathway for fatty acid oxidation regulates hematopoietic stem cell maintenance. Nature Med. 18, 1350\u20131358 (2012)","journal-title":"Nature Med."},{"key":"BFnature15248_CR33","doi-asserted-by":"publisher","first-page":"2318","DOI":"10.1038\/sj.leu.2403135","volume":"17","author":"J Gabert","year":"2003","unstructured":"Gabert, J. et al. Standardization and quality control studies of 'real-time' quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia \u2014 a Europe Against Cancer program. Leukemia 17, 2318\u20132357 (2003)","journal-title":"Leukemia"},{"key":"BFnature15248_CR34","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1038\/sj.gt.3301292","volume":"7","author":"D N\u00e8gre","year":"2000","unstructured":"N\u00e8gre, D. et al. Characterization of novel safe lentiviral vectors derived from simian immunodeficiency virus (SIVmac251) that efficiently transduce mature human dendritic cells. Gene Ther. 7, 1613\u20131623 (2000)","journal-title":"Gene Ther."},{"key":"BFnature15248_CR35","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.cca.2009.10.007","volume":"411","author":"O Roth","year":"2010","unstructured":"Roth, O. et al. Imatinib assay by HPLC with photodiode-array UV detection in plasma from patients with chronic myeloid leukemia: comparison with LC-MS\/MS. Clin. Chim acta. 411, 140\u2013146 (2010)","journal-title":"Clin. Chim acta."},{"key":"BFnature15248_CR36","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1158\/0008-5472.CAN-09-1947","volume":"70","author":"TC Chou","year":"2010","unstructured":"Chou, T. C. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Res. 70, 440\u2013446 (2010)","journal-title":"Cancer Res."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature15248.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature15248","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature15248.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T18:35:00Z","timestamp":1684434900000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature15248"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,9]]},"references-count":36,"journal-issue":{"issue":"7569","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["BFnature15248"],"URL":"https:\/\/doi.org\/10.1038\/nature15248","relation":{},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,9]]},"assertion":[{"value":"17 March 2014","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2015","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}