title: MN1-Fli1 oncofusion transforms murine hematopoietic progenitor cells into acute megakaryoblastic leukemia cells.
abstract: Long-term outcome of acute megakaryoblastic leukemia (AMKL) patients without Down's syndrome remains poor. Founding mutations and chimeric oncogenes characterize various AMKL subtypes. However, for around one third of all cases the underlying mechanisms of AMKL leukemogenesis are still largely unknown. Recently, an in-frame fusion of meningeoma 1-friend leukemia virus integration 1 (MN1-Fli1) gene was detected in a child with AMKL. We intended to investigate the potential role of this oncofusion in leukemogenesis of acute myeloid leukemia. Strikingly, expression of MN1-Fli1 in murine hematopoietic progenitor cells was sufficient to induce leukemic transformation generating immature myeloid cells with cytomorphology and expression of surface markers typical for AMKL. Systematic structure function analyses revealed FLS and 3'ETS domains of Fli1 as decisive domains for the AMKL phenotype. Our data highlight an important role of MN1-Fli1 in AMKL leukemogenesis and provide a basis for research assessing the value of this oncofusion as a future diagnostic marker and/or therapeutic target in AMKL patients.
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: D V
authors.initials: DV
authors.lastname: Wenge
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Felipe-Fumero
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Angenendt
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schliemann
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schmidt
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: L H
authors.initials: LH
authors.lastname: Schmidt
authors.affiliation: Department of Medicine I, University of Dresden, Dresden, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Thiede
authors.affiliation: Department of Medicine I, University of Dresden, Dresden, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Ehninger
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: W E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: M-F
authors.initials: MF
authors.lastname: Arteaga
authors.affiliation: Department of Medicine A, Hematology and Oncology, University of Münster, Münster, Germany.
authors.forename: J-H
authors.initials: JH
authors.lastname: Mikesch