Tyrosine kinase inhibitors bind and inhibit cytosolic FGFR1 fusion dimer phosphorylation

Stable Identifier
Reaction [binding]
Homo sapiens
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In a murine mouse model of ZNF198-FGFR1-induced EMS, treatment with the FGFR-inhibitor Midostaurin (PKC412) resulted in prolonged survival (Chen, 2004). Similarly, growth of ZNF-198-FGFR1-, FGFR1OP2-FGFR1-, and BCR-FGFR1-expressing lines is blocked by treatment with FGFR-inhibitors (Demiroglu, 2001; Gu, 2006; Chase, 2007; Zhen, 2007; Wasag, 2011).

Literature References
PubMed ID Title Journal Year
16946300 Phosphotyrosine profiling identifies the KG-1 cell line as a model for the study of FGFR1 fusions in acute myeloid leukemia

Macneill, J, Gu, TL, Walters, DK, Nardone, J, Polakiewicz, RD, Wang, Y, Popova, L, Rush, J, Comb, MJ, Reeves, C, Druker, BJ, Goss, VL

Blood 2006
11739186 The t(8;22) in chronic myeloid leukemia fuses BCR to FGFR1: transforming activity and specific inhibition of FGFR1 fusion proteins

Doody, ML, Demiroglu, A, Carnicero, F, Brody, JP, Melo, JV, Koduru, P, Cross, NC, Heath, C, Hawson, G, Taylor, K, Steer, EJ, Goldman, JM, Reiter, A, Rodwell, R, Bentley, M, Allen, SL

Blood 2001
15448205 PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder

Gilliland, DG, Cohen, S, Huntly, B, Galinsky, I, Xiao, S, Duclos, N, Fabbro, D, Kutok, JL, Stone, RM, Fletcher, JA, Roesel, J, Okabe, R, Lee, BH, Chen, J, Banerji, L, Adelsperger, J, Wadleigh, M, Williams, IR, Deangelo, DJ, Meyer, T, Cohen, PS, Griffin, JD, Coburn, A

Proc Natl Acad Sci U S A 2004
17698633 Activity of TKI258 against primary cells and cell lines with FGFR1 fusion genes associated with the 8p11 myeloproliferative syndrome

Grand, FH, Cross, NC, Chase, A

Blood 2007
17533378 Indirubin-3'-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2 activity via p38 MAPK

Sørensen, V, Wied?ocha, A, Jin, Y, Zhen, Y, Suo, Z

Oncogene 2007
21330321 The kinase inhibitor TKI258 is active against the novel CUX1-FGFR1 fusion detected in a patient with T-lymphoblastic leukemia/lymphoma and t(7;8)(q22;p11)

Wasag, B, Vandenberghe, P, Meeus, P, Lierman, E, Cools, J

Haematologica 2011
Functional status

Gain of function of cytosolic FGFR1 fusion mutant dimers [cytosol]

Disease Entity
Name Identifier Synonyms
subacute leukemia DOID:3264
myelodysplastic myeloproliferative cancer DOID:4972 Myeloproliferative/Myelodysplastic syndromes, unclassifiable myelodysplastic myeloproliferative disease, Unclassifiable Myeloproliferative/Myelodysplastic syndrome, Myelodysplastic/myeloproliferative disease (morphologic abnormality)
acute lymphocytic leukemia DOID:9952
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
chronic myeloid leukemia DOID:8552 CML, chronic myelogenous leukemia, no ICD-O subtype (morphologic abnormality), chronic myeloid leukemia, disease (disorder), chronic myeloid leukemia without mention of remission, CML - chronic Myelogenous Leukemia, chronic myeloid leukemia in remission (disorder), Myeloid Leukemia, chronic, CML in Remission, chronic myeloid leukemia in remission, chronic myeloid leukaemia, chronic myeloid leukemia NOS (disorder)
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