Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic Classification and Prognosis in Acute Myeloid Leukemia. N Engl J Med. 2016;374(23):2209–21.
Article
CAS
Google Scholar
Ley TJ, Miller C, Ding L, Raphael BJ, Mungall AJ, Robertson A, et al. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74.
Article
Google Scholar
Janke H, Pastore F, Schumacher D, Herold T, Hopfner KP, Schneider S, et al. Activating FLT3 mutants show distinct gain-of-function phenotypes in vitro and a characteristic signaling pathway profile associated with prognosis in acute myeloid leukemia. PLoS ONE. 2014;9(3): e89560.
Article
Google Scholar
Choudhary C, Schwäble J, Brandts C, Tickenbrock L, Sargin B, Kindler T, et al. AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations. Blood. 2005;106(1):265–73.
Article
CAS
Google Scholar
Thiede C, Steudel C, Mohr B, Schaich M, Schäkel U, Platzbecker U, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002;99(12):4326–35.
Article
CAS
Google Scholar
Rücker FG, Du L, Luck TJ, Benner A, Krzykalla J, Gathmann I, et al. Molecular landscape and prognostic impact of FLT3-ITD insertion site in acute myeloid leukemia: RATIFY study results. Leukemia. 2022;36(1):90–9.
Article
Google Scholar
Wagner K, Damm F, Thol F, Göhring G, Görlich K, Heuser M, et al. FLT3-internal tandem duplication and age are the major prognostic factors in patients with relapsed acute myeloid leukemia with normal karyotype. Haematologica. 2011;96(5):681–6.
Article
Google Scholar
Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299–312.
Article
CAS
Google Scholar
Wang Z, Cai J, Cheng J, Yang W, Zhu Y, Li H, et al. FLT3 Inhibitors in Acute Myeloid Leukemia: Challenges and Recent Developments in Overcoming Resistance. J Med Chem. 2021;64(6):2878–900.
Article
CAS
Google Scholar
Gebru MT, Wang HG. Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia. J Hematol Oncol. 2020;13(1):155.
Article
Google Scholar
Perl AE, Martinelli G, Cortes JE, Neubauer A, Berman E, Paolini S, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019;381(18):1728–40.
Article
CAS
Google Scholar
Zhao JC, Agarwal S, Ahmad H, Amin K, Bewersdorf JP, Zeidan AM. A review of FLT3 inhibitors in acute myeloid leukemia. Blood Rev. 2022;52: 100905.
Article
CAS
Google Scholar
Sung PJ, Sugita M, Koblish H, Perl AE, Carroll M. Hematopoietic cytokines mediate resistance to targeted therapy in FLT3-ITD acute myeloid leukemia. Blood Adv. 2019;3(7):1061–72.
Article
CAS
Google Scholar
Ghiaur G, Levis M. Mechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment. Hematol Oncol Clin North Am. 2017;31(4):681–92.
Article
Google Scholar
Joshi SK, Nechiporuk T, Bottomly D, Piehowski PD, Reisz JA, Pittsenbarger J, et al. The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance. Cancer Cell. 2021;39(7):999-1014.e8.
Article
CAS
Google Scholar
Alotaibi AS, Yilmaz M, Kanagal-Shamanna R, Loghavi S, Kadia TM, DiNardo CD, et al. Patterns of resistance differ in patients with acute myeloid leukemia treated with type I versus type II FLT3 inhibitors. Blood Cancer Discov. 2021;2(2):125–34.
Article
CAS
Google Scholar
Smith CC, Wang Q, Chin CS, Salerno S, Damon LE, Levis MJ, et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature. 2012;485(7397):260–3.
Article
CAS
Google Scholar
McMahon CM, Ferng T, Canaani J, Wang ES, Morrissette J, Eastburn DJ, et al. Clonal selection with RAS pathway activation mediates secondary clinical resistance to Selective FLT3 inhibition in acute myeloid leukemia. Cancer Discov. 2019;9(8):1050–63.
Article
CAS
Google Scholar
Smith CC, Levis MJ, Perl AE, Hill JE, Rosales M, Bahceci E. Molecular profile of FLT3-mutated relapsed/refractory patients with AML in the phase 3 ADMIRAL study of gilteritinib. Blood Adv. 2022;6(7):2144–55.
Article
CAS
Google Scholar
Eguchi M, Minami Y, Kuzume A, Chi S. Mechanisms underlying resistance to FLT3 inhibitors in acute myeloid leukemia. Biomedicines. 2020;8(8):245.
Article
CAS
Google Scholar
Patwardhan PP, Ivy KS, Musi E, de Stanchina E, Schwartz GK. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma. Oncotarget. 2016;7(4):4093–109.
Article
Google Scholar
Du W, Huang H, Sorrelle N, Brekken RA. Sitravatinib potentiates immune checkpoint blockade in refractory cancer models. JCI Insight. 2018;3(21):e124184.
Article
Google Scholar
Msaouel P, Goswami S, Thall PF, Wang X, Yuan Y, Jonasch E, et al. A phase 1–2 trial of sitravatinib and nivolumab in clear cell renal cell carcinoma following progression on antiangiogenic therapy. Sci Transl Med. 2022;14(641):eabm6420.
Article
CAS
Google Scholar
Dolan M, Mastri M, Tracz A, Christensen JG, Chatta G, Ebos J. Enhanced efficacy of sitravatinib in metastatic models of antiangiogenic therapy resistance. PLoS ONE. 2019;14(8): e0220101.
Article
CAS
Google Scholar
Oliva M, Chepeha D, Araujo DV, Diaz-Mejia JJ, Olson P, Prawira A, et al. Antitumor immune effects of preoperative sitravatinib and nivolumab in oral cavity cancer: SNOW window-of-opportunity study. J Immunother Cancer. 2021;9(10):e003476.
Zimmerman EI, Turner DC, Buaboonnam J, Hu S, Orwick S, Roberts MS, et al. Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia. Blood. 2013;122(22):3607–15.
Article
CAS
Google Scholar
Mori M, Kaneko N, Ueno Y, Yamada M, Tanaka R, Saito R, et al. Gilteritinib, a FLT3/AXL inhibitor, shows antileukemic activity in mouse models of FLT3 mutated acute myeloid leukemia. Invest New Drugs. 2017;35(5):556–65.
Article
CAS
Google Scholar
Jafari R, Almqvist H, Axelsson H, Ignatushchenko M, Lundbäck T, Nordlund P, et al. The cellular thermal shift assay for evaluating drug target interactions in cells. Nat Protoc. 2014;9(9):2100–22.
Article
CAS
Google Scholar
Dumas PY, Villacreces A, Guitart AV, El-Habhab A, Massara L, Mansier O, et al. Dual inhibition of FLT3 and AXL by gilteritinib overcomes hematopoietic niche-driven resistance mechanisms in FLT3-ITD acute myeloid leukemia. Clin Cancer Res. 2021;27(21):6012–25.
Article
CAS
Google Scholar
He X, Zhu Y, Lin YC, Li M, Du J, Dong H, et al. PRMT1-mediated FLT3 arginine methylation promotes maintenance of FLT3-ITD(+) acute myeloid leukemia. Blood. 2019;134(6):548–60.
Article
CAS
Google Scholar
Zarrinkar PP, Gunawardane RN, Cramer MD, Gardner MF, Brigham D, Belli B, et al. AC220 is a uniquely potent and selective inhibitor of FLT3 for the treatment of acute myeloid leukemia (AML). Blood. 2009;114(14):2984–92.
Article
CAS
Google Scholar
Bauer T, Cho BC, Heist R, Bazhenova L, Werner T, Goel S, et al. First-in-human phase 1/1b study to evaluate sitravatinib in patients with advanced solid tumors. Invest New Drugs. 2022;40(5):990–1000.
Article
CAS
Google Scholar
Perl AE, Altman JK, Cortes J, Smith C, Litzow M, Baer MR, et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1–2 study. Lancet Oncol. 2017;18(8):1061–75.
Article
CAS
Google Scholar
Antar AI, Otrock ZK, Jabbour E, Mohty M, Bazarbachi A. FLT3 inhibitors in acute myeloid leukemia: ten frequently asked questions. Leukemia. 2020;34(3):682–96.
Article
Google Scholar
Tarver TC, Hill JE, Rahmat L, Perl AE, Bahceci E, Mori K, et al. Gilteritinib is a clinically active FLT3 inhibitor with broad activity against FLT3 kinase domain mutations. Blood Adv. 2020;4(3):514–24.
Article
CAS
Google Scholar
Zorn JA, Wang Q, Fujimura E, Barros T, Kuriyan J. Crystal structure of the FLT3 kinase domain bound to the inhibitor Quizartinib (AC220). PLoS ONE. 2015;10(4): e0121177.
Article
Google Scholar
Ma J, Zhao S, Qiao X, Knight T, Edwards H, Polin L, et al. Inhibition of Bcl-2 synergistically enhances the antileukemic activity of midostaurin and gilteritinib in preclinical models of FLT3-mutated acute myeloid leukemia. Clin Cancer Res. 2019;25(22):6815–26.
Article
CAS
Google Scholar
Newell LF, Cook RJ. Advances in acute myeloid leukemia. BMJ. 2021;375: n2026.
Article
Google Scholar
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47.
Article
Google Scholar
Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 Mutation. N Engl J Med. 2017;377(5):454–64.
Article
CAS
Google Scholar
Cortes JE, Khaled S, Martinelli G, Perl AE, Ganguly S, Russell N, et al. Quizartinib versus salvage chemotherapy in relapsed or refractory FLT3-ITD acute myeloid leukaemia (QuANTUM-R): a multicentre, randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2019;20(7):984–97.
Article
CAS
Google Scholar
Cortes J, Perl AE, Döhner H, Kantarjian H, Martinelli G, Kovacsovics T, et al. Quizartinib, an FLT3 inhibitor, as monotherapy in patients with relapsed or refractory acute myeloid leukaemia: an open-label, multicentre, single-arm, phase 2 trial. Lancet Oncol. 2018;19(7):889–903.
Article
CAS
Google Scholar
Alvarado Y, Kantarjian HM, Luthra R, Ravandi F, Borthakur G, Garcia-Manero G, et al. Treatment with FLT3 inhibitor in patients with FLT3-mutated acute myeloid leukemia is associated with development of secondary FLT3-tyrosine kinase domain mutations. Cancer. 2014;120(14):2142–9.
Article
CAS
Google Scholar
von Bubnoff N, Engh RA, Aberg E, Sänger J, Peschel C, Duyster J. FMS-like tyrosine kinase 3-internal tandem duplication tyrosine kinase inhibitors display a nonoverlapping profile of resistance mutations in vitro. Cancer Res. 2009;69(7):3032–41.
Article
Google Scholar
Scholl S, Fleischmann M, Schnetzke U, Heidel FH. Molecular mechanisms of resistance to FLT3 inhibitors in acute myeloid leukemia: ongoing challenges and future treatments. Cells. 2020;9(11):2493.
Article
CAS
Google Scholar
Kiyoi H, Kawashima N, Ishikawa Y. FLT3 mutations in acute myeloid leukemia: therapeutic paradigm beyond inhibitor development. Cancer Sci. 2020;111(2):312–22.
Article
CAS
Google Scholar
Lam S, Leung A. Overcoming resistance to FLT3 inhibitors in the Treatment of FLT3-mutated AML. Int J Mol Sci. 2020;21(4):1537.
Article
CAS
Google Scholar
Sato T, Yang X, Knapper S, White P, Smith BD, Galkin S, et al. FLT3 ligand impedes the efficacy of FLT3 inhibitors in vitro and in vivo. Blood. 2011;117(12):3286–93.
Article
CAS
Google Scholar
Traer E, Martinez J, Javidi-Sharifi N, Agarwal A, Dunlap J, English I, et al. FGF2 from marrow microenvironment promotes resistance to FLT3 inhibitors in acute myeloid leukemia. Cancer Res. 2016;76(22):6471–82.
Article
CAS
Google Scholar
Park IK, Mishra A, Chandler J, Whitman SP, Marcucci G, Caligiuri MA. Inhibition of the receptor tyrosine kinase Axl impedes activation of the FLT3 internal tandem duplication in human acute myeloid leukemia: implications for Axl as a potential therapeutic target. Blood. 2013;121(11):2064–73.
Article
CAS
Google Scholar
Park IK, Mundy-Bosse B, Whitman SP, Zhang X, Warner SL, Bearss DJ, et al. Receptor tyrosine kinase Axl is required for resistance of leukemic cells to FLT3-targeted therapy in acute myeloid leukemia. Leukemia. 2015;29(12):2382–9.
Article
CAS
Google Scholar
Dumas PY, Naudin C, Martin-Lannerée S, Izac B, Casetti L, Mansier O, et al. Hematopoietic niche drives FLT3-ITD acute myeloid leukemia resistance to quizartinib via STAT5-and hypoxia-dependent upregulation of AXL. Haematologica. 2019;104(10):2017–27.
Article
CAS
Google Scholar
Yang Y, Ji N, Cai CY, Wang JQ, Lei ZN, Teng QX, et al. Modulating the function of ABCB1: in vitro and in vivo characterization of sitravatinib, a tyrosine kinase inhibitor. Cancer Commun (Lond). 2020;40(7):285–300.
Article
Google Scholar
Wu CP, Hsiao SH, Huang YH, Hung LC, Yu YJ, Chang YT, et al. Sitravatinib sensitizes ABCB1- and ABCG2-overexpressing multidrug-resistant cancer cells to chemotherapeutic drugs. Cancers (Basel). 2020;12(1):195.
Article
CAS
Google Scholar