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References
McKenna HJ, Stocking KL, Miller RE, Brasel K, De Smedt T, Maraskovsky E et al. Mice lacking flt3 ligand have deficient hematopoiesis affecting hematopoietic progenitor cells, dendritic cells, and natural killer cells. Blood 2000; 95: 3489–3497.
Mackarehtschian K, Hardin JD, Moore KA, Boast S, Goff SP, Lemischka IR . Targeted disruption of the flk2/flt3 gene leads to deficiencies in primitive hematopoietic progenitors. Immunity 1995; 3: 147–161.
Kayser S, Schlenk RF, Londono MC, Breitenbuecher F, Wittke K, Du J et al. Insertion of FLT3 internal tandem duplication in the tyrosine kinase domain-1 is associated with resistance to chemotherapy and inferior outcome. Blood 2009; 114: 2386–2392.
Reindl C, Bagrintseva K, Vempati S, Schnittger S, Ellwart JW, Wenig K et al. Point mutations in the juxtamembrane domain of FLT3 define a new class of activating mutations in AML. Blood 2006; 107: 3700–3707.
Deeb KK, Smonskey MT, DeFedericis H, Deeb G, Sait SNJ, Wetzler M et al. Deletion and deletion/insertion mutations in the juxtamembrane domain of the FLT3 gene in adult acute myeloid leukemia. Leuk Res Rep 2014; 3: 86–89.
Griffith J, Black J, Faerman C, Swenson L, Wynn M, Lu F et al. The structural basis for autoinhibition of FLT3 by the juxtamembrane domain. Mol Cell 2004; 13: 169–178.
Kiyoi H, Ohno R, Ueda R, Saito H, Naoe T . Mechanism of constitutive activation of FLT3 with internal tandem duplication in the juxtamembrane domain. Oncogene 2002; 21: 2555–2563.
Li L, Bailey E, Greenblatt S, Huso D, Small D . Loss of the wild-type allele contributes to myeloid expansion and disease aggressiveness in FLT3/ITD knockin mice. Blood 2011; 118: 4935–4945.
Rocnik JL, Okabe R, Yu J, Lee BH, Giese N, Schenkein DP et al. Roles of tyrosine 589 and 591 in STAT5 activation and transformation mediated by FLT3-ITD. Blood 2006; 108: 1339–1345.
Fröhling S, Scholl C, Levine RL, Loriaux M, Boggon TJ, Bernard OA et al. Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles. Cancer Cell 2007; 12: 501–513.
Choudhary C, Olsen JV, Brandts C, Cox J, Reddy PNG, Böhmer FD et al. Mislocalized activation of oncogenic RTKs switches downstream signaling outcomes. Mol Cell 2009; 36: 326–339.
Rahmani M, Aust MM, Attkisson E, Williams DC, Ferreira-Gonzalez A, Grant S . Dual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism. Cancer Res 2013; 73: 1340–1351.
Armstrong SA, Mabon ME, Silverman LB, Li A, Gribben JG, Fox EA . FLT3 mutations in childhood acute lymphoblastic leukemia. Blood 2004; 103: 3544–3546.
Chang P, Kang M, Xiao A, Chang J, Feusner J, Buffler P et al. FLT3 mutation incidence and timing of origin in a population case series of pediatric leukemia. BMC Cancer 2010; 10: 513.
Kim TW, Lee H, Kang Y, Choe MS, Ryu M, Chang HM et al. Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors. Clin Cancer Res 2004; 10: 3076–3081.
Acknowledgements
We thank Kristina Feldberg for expert technical assistance. We acknowledge Frank D Böhmer for providing the pcDNA3-FLT3 (WT)-HA vector and M-D Hagel for initial cloning of vectors. This work was in part supported by the Novartis Foundation.
Author contribution
NC, RCP, GR, JR, PC, MS, TH, THB, SS and SK designed research. NC, GR, RCP and JR performed research. NC, GR, RCP, PC, TH, SS and SK analyzed data. NC, RCP, GR, SS and SK wrote the paper.
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SK has received honoraria for consultancy from Novartis, Pfizer, Brystol-Meyers Squibb, and Ariad. TH and SS have equity ownership of MLL. THB has received honoraria for consultancy from Novartis, Pfizer, Brystol-Meyers Squibb. The remaining authors declare no conflict of interest.
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Chatain, N., Perera, R., Rossetti, G. et al. Rare FLT3 deletion mutants may provide additional treatment options to patients with AML: an approach to individualized medicine. Leukemia 29, 2434–2438 (2015). https://doi.org/10.1038/leu.2015.131
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DOI: https://doi.org/10.1038/leu.2015.131
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