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Sci.<\/i>, <b>19<\/b>, 3198 (2018).","DOI":"10.3390\/ijms19103198"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5) Fathi AT, Chen YB. The role of FLT 3 inhibitors in the treatment of FLT 3-mutated acute myeloid leukemia. <i>Eur. J. Haematol.<\/i>, <b>98<\/b>, 330\u2013336 (2017).","DOI":"10.1111\/ejh.12841"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Kiyoi H, Naoe T. FLT3 in human hematologic malignancies. <i>Leuk. Lymphoma<\/i>, <b>43<\/b>, 1541\u20131547 (2002).","DOI":"10.1080\/1042819021000002866"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Leick MB, Levis MJ. The future of targeting FLT3 activation in AML. <i>Curr. Hematol. Malig. 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Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia. <i>Blood<\/i>, <b>108<\/b>, 2358\u20132365 (2006).","DOI":"10.1182\/blood-2006-02-003475"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Rocnik JL, Okabe R, Yu J-C, Lee BH, Giese N, Schenkein DP, Gilliland DG. Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. <i>Blood<\/i>, <b>108<\/b>, 1339\u20131345 (2006).","DOI":"10.1182\/blood-2005-11-011429"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Larrosa-Garcia M, Baer MR. FLT3 inhibitors in acute myeloid leukemia: current status and future directions. <i>Mol. 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AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). <i>Blood<\/i>, <b>114<\/b>, 2984\u20132992 (2009).","DOI":"10.1182\/blood-2009-05-222034"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Weisberg E, Sattler M, Ray A, Griffin J. Drug resistance in mutant FLT3-positive AML. <i>Oncogene<\/i>, <b>29<\/b>, 5120\u20135134 (2010).","DOI":"10.1038\/onc.2010.273"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17) Smith CC, Lin K, Stecula A, Sali A, Shah NP. FLT3 D835 mutations confer differential resistance to type II FLT3 inhibitors. <i>Leukemia<\/i>, <b>29<\/b>, 2390\u20132392 (2015).","DOI":"10.1038\/leu.2015.165"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18) Bagrintseva K, Geisenhof S, Kern R, Eichenlaub S, Reindl C, Ellwart JW, Hiddemann W, Spiekermann K. 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