{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:29:50Z","timestamp":1792639790496,"version":"4.5.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T00:00:00Z","timestamp":1682035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["P30 CA016672"],"award-info":[{"award-number":["P30 CA016672"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Leukemia"],"published-print":{"date-parts":[[2023,6]]},"DOI":"10.1038\/s41375-023-01897-x","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T15:47:53Z","timestamp":1682092073000},"page":"1379-1383","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["FLT3 inhibitors upregulate CXCR4 and E-selectin ligands via ERK suppression in AML cells and CXCR4\/E-selectin inhibition enhances anti-leukemia efficacy of FLT3-targeted therapy in AML"],"prefix":"10.1038","volume":"37","author":[{"given":"Yannan","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahesh","family":"Basyal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3330-2174","authenticated-orcid":false,"given":"Lauren","family":"Ostermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-9074","authenticated-orcid":false,"given":"Jared K.","family":"Burks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlie","family":"Ly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Mu-Mosley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7918-8952","authenticated-orcid":false,"given":"Qi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Fogler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Magnani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Lesegretain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna A.","family":"Zal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Zal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1144-1958","authenticated-orcid":false,"given":"Michael","family":"Andreeff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,4,21]]},"reference":[{"key":"1897_CR1","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1080\/1042819031000067503","volume":"44","author":"PD Kottaridis","year":"2003","unstructured":"Kottaridis PD, Gale RE, Linch DC. Prognostic implications of the presence of FLT3 mutations in patients with acute myeloid leukemia. Leuk Lymphoma. 2003;44:905\u201313.","journal-title":"Leuk Lymphoma"},{"key":"1897_CR2","doi-asserted-by":"publisher","first-page":"612880","DOI":"10.3389\/fonc.2020.612880","volume":"10","author":"VE Kennedy","year":"2020","unstructured":"Kennedy VE, Smith CC. FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies. Front Oncol. 2020;10:612880.","journal-title":"Front Oncol"},{"key":"1897_CR3","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1093\/jnci\/djm328","volume":"100","author":"W Zhang","year":"2008","unstructured":"Zhang W, Konopleva M, Shi YX, McQueen T, Harris D, Ling X, et al. Mutant FLT3: a direct target of sorafenib in acute myelogenous leukemia. J Natl Cancer Inst. 2008;100:184\u201398.","journal-title":"J Natl Cancer Inst"},{"key":"1897_CR4","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1007\/s11899-015-0253-6","volume":"10","author":"Y Tabe","year":"2015","unstructured":"Tabe Y, Konopleva M. Role of microenvironment in resistance to therapy in AML. Curr Hematol Malig Rep. 2015;10:96\u2013103.","journal-title":"Curr Hematol Malig Rep"},{"key":"1897_CR5","doi-asserted-by":"publisher","first-page":"1901","DOI":"10.1182\/blood-2005-04-1417","volume":"106","author":"T Lapidot","year":"2005","unstructured":"Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood. 2005;106:1901\u201310.","journal-title":"Blood"},{"key":"1897_CR6","doi-asserted-by":"publisher","first-page":"1651","DOI":"10.1038\/nm.2969","volume":"18","author":"IG Winkler","year":"2012","unstructured":"Winkler IG, Barbier V, Nowlan B, Jacobsen RN, Forristal CE, Patton JT, et al. Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat Med. 2012;18:1651\u20137.","journal-title":"Nat Med"},{"key":"1897_CR7","doi-asserted-by":"publisher","first-page":"5510","DOI":"10.1073\/pnas.92.12.5510","volume":"92","author":"GL Wang","year":"1995","unstructured":"Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA. 1995;92:5510\u20134.","journal-title":"Proc Natl Acad Sci USA"},{"key":"1897_CR8","doi-asserted-by":"publisher","first-page":"786","DOI":"10.1182\/blood-2006-05-024844","volume":"109","author":"AC Spoo","year":"2007","unstructured":"Spoo AC, Lubbert M, Wierda WG, Burger JA. CXCR4 is a prognostic marker in acute myelogenous leukemia. Blood. 2007;109:786\u201391.","journal-title":"Blood"},{"key":"1897_CR9","doi-asserted-by":"publisher","first-page":"6857","DOI":"10.3390\/ijms22136857","volume":"22","author":"S Bruno","year":"2021","unstructured":"Bruno S, Mancini M, De Santis S, Monaldi C, Cavo M, Soverini S. The role of hypoxic bone marrow microenvironment in acute myeloid leukemia and future therapeutic opportunities. Int J Mol Sci. 2021;22:6857.","journal-title":"Int J Mol Sci"},{"key":"1897_CR10","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1002\/cncr.33338","volume":"127","author":"G Borthakur","year":"2021","unstructured":"Borthakur G, Ofran Y, Tallman MS, Foran J, Uy GL, DiPersio JF, et al. BL-8040 CXCR4 antagonist is safe and demonstrates antileukemic activity in combination with cytarabine for the treatment of relapsed\/refractory acute myelogenous leukemia: an open-label safety and efficacy phase 2a study. Cancer. 2021;127:1246\u201359.","journal-title":"Cancer"},{"key":"1897_CR11","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1002\/cncr.11882","volume":"100","author":"J Crawford","year":"2004","unstructured":"Crawford J, Dale DC, Lyman GH. Chemotherapy-induced neutropenia: risks, consequences, and new directions for its management. Cancer. 2004;100:228\u201337.","journal-title":"Cancer"},{"key":"1897_CR12","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1080\/08977194.2018.1498487","volume":"36","author":"K Behrens","year":"2018","unstructured":"Behrens K, Alexander WS. Cytokine control of megakaryopoiesis. Growth Factors. 2018;36:89\u2013103.","journal-title":"Growth Factors"},{"key":"1897_CR13","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1038\/sj.leu.2401081","volume":"12","author":"N Brouard","year":"1998","unstructured":"Brouard N, Chapel A, Neildez-Nguyen TM, Granotier C, Khazaal I, Peault B, et al. Transplantation of stromal cells transduced with the human IL3 gene to stimulate hematopoiesis in human fetal bone grafts in non-obese, diabetic-severe combined immunodeficiency mice. Leukemia. 1998;12:1128\u201335.","journal-title":"Leukemia"},{"key":"1897_CR14","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1055\/s-2007-1025445","volume":"203","author":"S Burdach","year":"1991","unstructured":"Burdach S. The granulocyte\/macrophage-colony stimulating factor (GM-CSF): basic science and clinical application. Klin Padiatr. 1991;203:302\u201310.","journal-title":"Klin Padiatr"},{"key":"1897_CR15","doi-asserted-by":"publisher","first-page":"e03445","DOI":"10.7554\/eLife.03445","volume":"3","author":"AA Warkentin","year":"2014","unstructured":"Warkentin AA, Lopez MS, Lasater EA, Lin K, He BL, Leung AY, et al. Overcoming myelosuppression due to synthetic lethal toxicity for FLT3-targeted acute myeloid leukemia therapy. Elife. 2014;3:e03445.","journal-title":"Elife"}],"container-title":["Leukemia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01897-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01897-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01897-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T17:10:49Z","timestamp":1686071449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41375-023-01897-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,21]]},"references-count":15,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["1897"],"URL":"https:\/\/doi.org\/10.1038\/s41375-023-01897-x","relation":{},"ISSN":["0887-6924","1476-5551"],"issn-type":[{"value":"0887-6924","type":"print"},{"value":"1476-5551","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,21]]},"assertion":[{"value":"15 November 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 April 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 April 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"WEF and JLM are employees of GlycoMimetics. AL is an employee of Daiichi Sankyo, Inc. The other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}