{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:17:00Z","timestamp":1791353820177,"version":"4.3.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2009,6,7]],"date-time":"2009-06-07T00:00:00Z","timestamp":1244332800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nat Genet"],"published-print":{"date-parts":[[2009,7]]},"DOI":"10.1038\/ng.389","type":"journal-article","created":{"date-parts":[[2009,6,8]],"date-time":"2009-06-08T10:18:49Z","timestamp":1244456329000},"page":"783-792","source":"Crossref","is-referenced-by-count":262,"title":["Loss of the Alox5 gene impairs leukemia stem cells and prevents chronic myeloid leukemia"],"prefix":"10.1038","volume":"41","author":[{"given":"Yaoyu","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiguo","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoguang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2009,6,7]]},"reference":[{"key":"BFng389_CR1","doi-asserted-by":"publisher","first-page":"3983","DOI":"10.1073\/pnas.0530291100","volume":"100","author":"M Al-Hajj","year":"2003","unstructured":"Al-Hajj, M., Wicha, M.S., Benito-Hernandez, A., Morrison, S.J. & Clarke, M.F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl. Acad. Sci. USA 100, 3983\u20133988 (2003).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng389_CR2","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1056\/NEJMra061808","volume":"355","author":"CT Jordan","year":"2006","unstructured":"Jordan, C.T., Guzman, M.L. & Noble, M. Cancer stem cells. N. Engl. J. Med. 355, 1253\u20131261 (2006).","journal-title":"N. Engl. J. Med."},{"key":"BFng389_CR3","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1038\/nrc1232","volume":"3","author":"R Pardal","year":"2003","unstructured":"Pardal, R., Clarke, M.F. & Morrison, S.J. Applying the principles of stem-cell biology to cancer. Nat. Rev. Cancer 3, 895\u2013902 (2003).","journal-title":"Nat. Rev. Cancer"},{"key":"BFng389_CR4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/35102167","volume":"414","author":"T Reya","year":"2001","unstructured":"Reya, T., Morrison, S.J., Clarke, M.F. & Weissman, I.L. Stem cells, cancer, and cancer stem cells. Nature 414, 105\u2013111 (2001).","journal-title":"Nature"},{"key":"BFng389_CR5","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.cell.2008.01.036","volume":"132","author":"DJ Rossi","year":"2008","unstructured":"Rossi, D.J., Jamieson, C.H. & Weissman, I.L. Stems cells and the pathways to aging and cancer. Cell 132, 681\u2013696 (2008).","journal-title":"Cell"},{"key":"BFng389_CR6","first-page":"5821","volume":"63","author":"SK Singh","year":"2003","unstructured":"Singh, S.K. et al. Identification of a cancer stem cell in human brain tumors. Cancer Res. 63, 5821\u20135828 (2003).","journal-title":"Cancer Res."},{"key":"BFng389_CR7","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.tcb.2005.07.004","volume":"15","author":"JC Wang","year":"2005","unstructured":"Wang, J.C. & Dick, J.E. Cancer stem cells: lessons from leukemia. Trends Cell Biol. 15, 494\u2013501 (2005).","journal-title":"Trends Cell Biol."},{"key":"BFng389_CR8","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1016\/j.ceb.2004.09.004","volume":"16","author":"AV Molofsky","year":"2004","unstructured":"Molofsky, A.V., Pardal, R. & Morrison, S.J. Diverse mechanisms regulate stem cell self-renewal. Curr. Opin. Cell Biol. 16, 700\u2013707 (2004).","journal-title":"Curr. Opin. Cell Biol."},{"key":"BFng389_CR9","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/nature01593","volume":"423","author":"T Reya","year":"2003","unstructured":"Reya, T. et al. A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423, 409\u2013414 (2003).","journal-title":"Nature"},{"key":"BFng389_CR10","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/35077219","volume":"411","author":"J Taipale","year":"2001","unstructured":"Taipale, J. & Beachy, P.A. The Hedgehog and Wnt signalling pathways in cancer. Nature 411, 349\u2013354 (2001).","journal-title":"Nature"},{"key":"BFng389_CR11","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1016\/j.ccr.2007.11.003","volume":"12","author":"C Zhao","year":"2007","unstructured":"Zhao, C. et al. Loss of beta-catenin impairs the renewal of normal and CML stem cells in vivo. Cancer Cell 12, 528\u2013541 (2007).","journal-title":"Cancer Cell"},{"key":"BFng389_CR12","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature01572","volume":"423","author":"J Lessard","year":"2003","unstructured":"Lessard, J. & Sauvageau, G. Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423, 255\u2013260 (2003).","journal-title":"Nature"},{"key":"BFng389_CR13","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1038\/nature01587","volume":"423","author":"IK Park","year":"2003","unstructured":"Park, I.K. et al. Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423, 302\u2013305 (2003).","journal-title":"Nature"},{"key":"BFng389_CR14","doi-asserted-by":"publisher","first-page":"1432","DOI":"10.1101\/gad.1299505","volume":"19","author":"AV Molofsky","year":"2005","unstructured":"Molofsky, A.V., He, S., Bydon, M., Morrison, S.J. & Pardal, R. Bmi-1 promotes neural stem cell self-renewal and neural development but not mouse growth and survival by repressing the p16Ink4a and p19Arf senescence pathways. Genes Dev. 19, 1432\u20131437 (2005).","journal-title":"Genes Dev."},{"key":"BFng389_CR15","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S0959-437X(02)00013-8","volume":"13","author":"SW Lowe","year":"2003","unstructured":"Lowe, S.W. & Sherr, C.J. Tumor suppression by Ink4a-Arf: progress and puzzles. Curr. Opin. Genet. Dev. 13, 77\u201383 (2003).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"BFng389_CR16","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1038\/nature04703","volume":"441","author":"OH Yilmaz","year":"2006","unstructured":"Yilmaz, O.H. et al. Pten dependence distinguishes haematopoietic stem cells from leukaemia-initiating cells. Nature 441, 475\u2013482 (2006).","journal-title":"Nature"},{"key":"BFng389_CR17","doi-asserted-by":"publisher","first-page":"730","DOI":"10.1038\/nm0797-730","volume":"3","author":"D Bonnet","year":"1997","unstructured":"Bonnet, D. & Dick, J.E. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat. Med. 3, 730\u2013737 (1997).","journal-title":"Nat. Med."},{"key":"BFng389_CR18","doi-asserted-by":"publisher","first-page":"645","DOI":"10.1038\/367645a0","volume":"367","author":"T Lapidot","year":"1994","unstructured":"Lapidot, T. et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 367, 645\u2013648 (1994).","journal-title":"Nature"},{"key":"BFng389_CR19","doi-asserted-by":"publisher","first-page":"5878","DOI":"10.1073\/pnas.0700460104","volume":"104","author":"MB Bowie","year":"2007","unstructured":"Bowie, M.B. et al. Identification of a new intrinsically timed developmental checkpoint that reprograms key hematopoietic stem cell properties. Proc. Natl. Acad. Sci. USA 104, 5878\u20135882 (2007).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng389_CR20","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ccr.2008.08.003","volume":"14","author":"C Dierks","year":"2008","unstructured":"Dierks, C. et al. Expansion of Bcr-Abl-positive leukemic stem cells is dependent on Hedgehog pathway activation. Cancer Cell 14, 238\u2013249 (2008).","journal-title":"Cancer Cell"},{"key":"BFng389_CR21","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1016\/j.ccr.2004.10.015","volume":"6","author":"BJ Huntly","year":"2004","unstructured":"Huntly, B.J. et al. MOZ-TIF2, but not BCR-ABL, confers properties of leukemic stem cells to committed murine hematopoietic progenitors. Cancer Cell 6, 587\u2013596 (2004).","journal-title":"Cancer Cell"},{"key":"BFng389_CR22","doi-asserted-by":"publisher","first-page":"2578","DOI":"10.1182\/blood-2007-02-073031","volume":"110","author":"SJ Neering","year":"2007","unstructured":"Neering, S.J. et al. Leukemia stem cells in a genetically defined murine model of blast-crisis CML. Blood 110, 2578\u20132585 (2007).","journal-title":"Blood"},{"key":"BFng389_CR23","doi-asserted-by":"publisher","first-page":"16870","DOI":"10.1073\/pnas.0606509103","volume":"103","author":"Y Hu","year":"2006","unstructured":"Hu, Y. et al. Targeting multiple kinase pathways in leukemic prognitors and stem cells is essential for improved treatment of Ph+ leukemia in mice. Proc. Natl. Acad. Sci. USA 103, 16870\u201316875 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng389_CR24","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":"BFng389_CR25","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/S0301-472X(00)00142-9","volume":"28","author":"SB Marley","year":"2000","unstructured":"Marley, S.B., Deininger, M.W., Davidson, R.J., Goldman, J.M. & Gordon, M.Y. The tyrosine kinase inhibitor STI571, like interferon-alpha, preferentially reduces the capacity for amplification of granulocyte-macrophage progenitors from patients with chronic myeloid leukemia. Exp. Hematol. 28, 551\u2013557 (2000).","journal-title":"Exp. Hematol."},{"key":"BFng389_CR26","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1038\/sj.emboj.7600502","volume":"24","author":"A Catalano","year":"2005","unstructured":"Catalano, A., Rodilossi, S., Caprari, P., Coppola, V. & Procopio, A. 5-Lipoxygenase regulates senescence-like growth arrest by promoting ROS-dependent p53 activation. EMBO J. 24, 170\u2013179 (2005).","journal-title":"EMBO J."},{"key":"BFng389_CR27","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/372179a0","volume":"372","author":"XS Chen","year":"1994","unstructured":"Chen, X.S., Sheller, J.R., Johnson, E.N. & Funk, C.D. Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase gene. Nature 372, 179\u2013182 (1994).","journal-title":"Nature"},{"key":"BFng389_CR28","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.tibs.2007.06.002","volume":"32","author":"O Radmark","year":"2007","unstructured":"Radmark, O., Werz, O., Steinhilber, D. & Samuelsson, B. 5-Lipoxygenase: regulation of expression and enzyme activity. Trends Biochem. Sci. 32, 332\u2013341 (2007).","journal-title":"Trends Biochem. Sci."},{"key":"BFng389_CR29","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1172\/JCI200318338","volume":"111","author":"RJ Soberman","year":"2003","unstructured":"Soberman, R.J. & Christmas, P. The organization and consequences of eicosanoid signaling. J. Clin. Invest. 111, 1107\u20131113 (2003).","journal-title":"J. Clin. Invest."},{"key":"BFng389_CR30","doi-asserted-by":"publisher","first-page":"5765","DOI":"10.1038\/sj.onc.1205702","volume":"21","author":"PM Taylor","year":"2002","unstructured":"Taylor, P.M. et al. Breast cancer cell-derived EMMPRIN stimulates fibroblast MMP2 release through a phospholipase A(2) and 5-lipoxygenase catalyzed pathway. Oncogene 21, 5765\u20135772 (2002).","journal-title":"Oncogene"},{"key":"BFng389_CR31","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/nrm2335","volume":"9","author":"MP Wymann","year":"2008","unstructured":"Wymann, M.P. & Schneiter, R. Lipid signalling in disease. Nat. Rev. Mol. Cell Biol. 9, 162\u2013176 (2008).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"BFng389_CR32","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1006\/abbi.2000.2168","volume":"385","author":"T Yokomizo","year":"2001","unstructured":"Yokomizo, T., Izumi, T. & Shimizu, T. Leukotriene B4: metabolism and signal transduction. Arch. Biochem. Biophys. 385, 231\u2013241 (2001).","journal-title":"Arch. Biochem. Biophys."},{"key":"BFng389_CR33","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1038\/nm1099","volume":"10","author":"L Zhao","year":"2004","unstructured":"Zhao, L. et al. The 5-lipoxygenase pathway promotes pathogenesis of hyperlipidemia-dependent aortic aneurysm. Nat. Med. 10, 966\u2013973 (2004).","journal-title":"Nat. Med."},{"key":"BFng389_CR34","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1084\/jem.189.9.1399","volume":"189","author":"S Li","year":"1999","unstructured":"Li, S., Ilaria, R.L. Jr, Million, R.P., Daley, G.Q. & Van Etten, R.A. The P190, P210, and p230 forms of the BCR\/ABL oncogene induce a similar chronic myeloid leukemia-like syndrome in mice but have different lymphoid leukemogenic activity. J. Exp. Med. 189, 1399\u20131412 (1999).","journal-title":"J. Exp. Med."},{"key":"BFng389_CR35","doi-asserted-by":"publisher","first-page":"1745","DOI":"10.1056\/NEJM199012203232506","volume":"323","author":"HR Knapp","year":"1990","unstructured":"Knapp, H.R. Reduced allergen-induced nasal congestion and leukotriene synthesis with an orally active 5-lipoxygenase inhibitor. N. Engl. J. Med. 323, 1745\u20131748 (1990).","journal-title":"N. Engl. J. Med."},{"key":"BFng389_CR36","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1128\/MCB.25.4.1215-1227.2005","volume":"25","author":"R Ferreira","year":"2005","unstructured":"Ferreira, R., Ohneda, K., Yamamoto, M. & Philipsen, S. GATA1 function, a paradigm for transcription factors in hematopoiesis. Mol. Cell. Biol. 25, 1215\u20131227 (2005).","journal-title":"Mol. Cell. Biol."},{"key":"BFng389_CR37","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/S0092-8674(00)80318-9","volume":"90","author":"AP Tsang","year":"1997","unstructured":"Tsang, A.P. et al. FOG, a multitype zinc finger protein, acts as a cofactor for transcription factor GATA-1 in erythroid and megakaryocytic differentiation. Cell 90, 109\u2013119 (1997).","journal-title":"Cell"},{"key":"BFng389_CR38","first-page":"203","volume":"15","author":"L Stenke","year":"1987","unstructured":"Stenke, L., Lauren, L., Reizenstein, P. & Lindgren, J.A. Leukotriene production by fresh human bone marrow cells: evidence of altered lipoxygenase activity in chronic myelocytic leukemia. Exp. Hematol. 15, 203\u2013207 (1987).","journal-title":"Exp. Hematol."},{"key":"BFng389_CR39","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1016\/S0301-472X(02)01026-3","volume":"31","author":"S Tornhamre","year":"2003","unstructured":"Tornhamre, S. et al. Inverse relationship between myeloid maturation and leukotriene C4 synthase expression in normal and leukemic myelopoiesis-consistent overexpression of the enzyme in myeloid cells from patients with chronic myeloid leukemia. Exp. Hematol. 31, 122\u2013130 (2003).","journal-title":"Exp. Hematol."},{"key":"BFng389_CR40","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1182\/blood-2006-10-054098","volume":"110","author":"C Peng","year":"2007","unstructured":"Peng, C. et al. Inhibition of heat shock protein 90 prolongs survival of mice with BCR-ABL-T315I-induced leukemia and suppresses leukemic stem cells. Blood 110, 678\u2013685 (2007).","journal-title":"Blood"},{"key":"BFng389_CR41","doi-asserted-by":"publisher","first-page":"3111","DOI":"10.1634\/stemcells.2007-0250","volume":"25","author":"SM Graham","year":"2007","unstructured":"Graham, S.M., Vass, J.K., Holyoake, T.L. & Graham, G.J. Transcriptional analysis of quiescent and proliferating CD34+ human hemopoietic cells from normal and chronic myeloid leukemia sources. Stem Cells 25, 3111\u20133120 (2007).","journal-title":"Stem Cells"},{"key":"BFng389_CR42","doi-asserted-by":"publisher","first-page":"2794","DOI":"10.1073\/pnas.0510423103","volume":"103","author":"JP Radich","year":"2006","unstructured":"Radich, J.P. et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc. Natl. Acad. Sci. USA 103, 2794\u20132799 (2006).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"BFng389_CR43","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1016\/0145-2126(95)00043-7","volume":"19","author":"KM Anderson","year":"1995","unstructured":"Anderson, K.M. et al. Selective inhibitors of 5-lipoxygenase reduce CML blast cell proliferation and induce limited differentiation and apoptosis. Leuk. Res. 19, 789\u2013801 (1995).","journal-title":"Leuk. Res."},{"key":"BFng389_CR44","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/ng1343","volume":"36","author":"Y Hu","year":"2004","unstructured":"Hu, Y. et al. Requirement of Src kinases Lyn, Hck and Fgr for BCR-ABL1-induced B-lymphoblastic leukemia but not chronic myeloid leukemia. Nat. Genet. 36, 453\u2013461 (2004).","journal-title":"Nat. Genet."},{"key":"BFng389_CR45","doi-asserted-by":"publisher","first-page":"6793","DOI":"10.1093\/emboj\/20.23.6793","volume":"20","author":"S Li","year":"2001","unstructured":"Li, S., Couvillon, A.D., Brasher, B.B. & Van Etten, R.A. Tyrosine phosphorylation of Grb2 by Bcr\/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling. EMBO J. 20, 6793\u20136804 (2001).","journal-title":"EMBO J."}],"container-title":["Nature Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ng.389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng.389","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ng.389.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T21:21:06Z","timestamp":1684444866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ng.389"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,6,7]]},"references-count":45,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2009,7]]}},"alternative-id":["BFng389"],"URL":"https:\/\/doi.org\/10.1038\/ng.389","relation":{},"ISSN":["1061-4036","1546-1718"],"issn-type":[{"value":"1061-4036","type":"print"},{"value":"1546-1718","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,6,7]]}}}