midostaurin-resistant FLT3 mutants don't bind midostaurin

Stable Identifier
Reaction [transition]
Homo sapiens
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The following FLT3 mutants are resistant to inhibition by the type I TKI midostaurin:
FLT3 Y591_V592insVDFREYEYDH (Knapper et al, 2006)
FLT3 A627P (Williams et al, 2013)
FLT3 N676D (partial: Albers et al, 2013)
FLT3 N676K (Heidel et al, 2006)
FLT3 F691I (Albers et al, 2013)
FLT3 F691L (partial: Baker et al, 2013; Williams et al, 2013)
Literature References
PubMed ID Title Journal Year
16868253 The effects of lestaurtinib (CEP701) and PKC412 on primary AML blasts: the induction of cytotoxicity varies with dependence on FLT3 signaling in both FLT3-mutated and wild-type cases

Gilkes, AF, Mills, KI, Austin, SJ, Burnett, AK, Knapper, S, Walsh, V

Blood 2006
23392356 The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib

Yu, C, Albers, C, Verbeek, M, Duyster, J, Leischner, H, Illert, AL, von Bubnoff, N, Peschel, C

Leukemia 2013
22858906 Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors

Nguyen, B, Brown, P, Li, L, Levis, M, Williams, AB, Leahy, D, Small, D

Leukemia 2013
23969938 Emergence of polyclonal FLT3 tyrosine kinase domain mutations during sequential therapy with sorafenib and sunitinib in FLT3-ITD-positive acute myeloid leukemia

Mullighan, CG, Baker, SD, Rubnitz, JE, Zimmerman, EI, Orwick, S, Inaba, H, Neale, GA, Zatechka, DS, Buaboonnam, J, Enemark, EJ, Shurtleff, S, Wang, YD, Olsen, SR

Clin. Cancer Res. 2013
16150941 Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain

Heidel, F, Serve, H, Solem, FK, Schiller, GJ, Breitenbuecher, F, Giles, F, Nimer, S, Wang, Y, Feldman, E, Kindler, T, Stone, RM, Thiede, MH, Huber, C, Brandts, C, Lipka, DB, Roesel, J, Kasper, S, Ehninger, G, Cohen, PS, Fischer, T

Blood 2006
Normal reaction
Functional status

Loss of function of midostaurin-resistant FLT3 mutants [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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