title: The new and recurrent FLT3 juxtamembrane deletion mutation shows a dominant negative effect on the wild-type FLT3 receptor.
abstract: In acute myeloid leukemia (AML), the Fms-like tyrosine kinase 3 (FLT3) is one of the most frequently mutated genes. Recently, a new and recurrent juxtamembrane deletion mutation (p.Q569Vfs*2) resulting in a truncated receptor was identified. The mutated receptor is expressed on the cell surface and still binds its ligand but loses the ability to activate ERK signaling. FLT3 p.Q569fs-expressing Ba/F3 cells show no proliferation after ligand stimulation. Furthermore, coexpressed with the FLT3 wild-type (WT) receptor, the truncated receptor suppresses stimulation and activation of the WT receptor. Thus, FLT3 p.Q569Vfs*2, to our knowledge, is the first FLT3 mutation with a dominant negative effect on the WT receptor.
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Sandhöfer
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Reiter
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Dufour
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Maja
authors.initials: M
authors.lastname: Rothenberg
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Nikola P
authors.initials: NP
authors.lastname: Konstandin
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Zellmeier
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Belay
authors.initials: B
authors.lastname: Tizazu
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Philipp A
authors.initials: PA
authors.lastname: Greif
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Metzeler
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hiddemann
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Polzer
authors.affiliation: Department of Internal Medicine III, University Hospital Grosshadern, Ludwig-Maximilians-University (LMU), Munich, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.|German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Spiekermann
mesh_terms: D045744:Cell Line, Tumor; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics* / Q000378:metabolism
chemical_list: C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3