Title: 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)
Authors: Wasag, Bartosz
Lierman, Els
Meeus, Peter
Cools, Jan
Vandenberghe, Peter # ×
Issue Date: Jun-2011
Publisher: Il Pensiero Scientifico
Series Title: Haematologica vol:96 issue:6 pages:922-926
Abstract: We report a patient with T-lymphoblastic leukemia/lymphoma and a t(7;8)(q22;p11). By fluorescence in situ hybridization and 5' RACE-PCR, CUX1 was identified as the fusion partner of FGFR1 in this case. We further investigated this novel FGFR1 fusion using the interleukin-3 (IL-3) dependent Ba/F3 cell line and demonstrated IL-3 independent cell growth of CUX1-FGFR1 expressing cells. TKI258 and PKC412 potently inhibited proliferation of CUX1-FGFR1 transformed Ba/F3 cells. This growth inhibition was shown to be mediated by inhibition of CUX1-FGFR1 kinase activity for TKI258 but not PKC412. In summary, we identified a novel CUX1-FGFR1 fusion oncogene in a patient with the 8p11 myeloproliferative syndrome and demonstrated its transforming potential in the Ba/F3 cell line. Our in vitro data support the further investigation of TKI258 for the treatment of constitutively active FGFR1 fusion proteins.
ISSN: 0390-6078
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Neurofibromatosis Research
Laboratory for Genetics of Malignant Disorders
Medicine Teaching Programs
× corresponding author
# (joint) last author

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