title: A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis.
abstract: The quest for novel therapeutic targets in acute myeloid leukemia (AML) is still ongoing. One of such targets, cyclin A1, was shown to be overexpressed in AML including AML stem cells. However, the function of cyclin A1 in AML is largely unknown, and the data on its impact on patients' survival remain controversial. Therefore, we developed a transgenic mouse model of stem cell-directed inducible cyclin A1 overexpression and crossed these mice with PML-RARα-knockin mice, which develop an AML M3-like phenotype. To observe the effects of cyclin A1 loss-of-function, we also crossed PML-RARα-knockin mice to cyclin A1-knockout mice. Neither overexpression nor loss of cyclin A1 significantly altered leukemogenesis in PML-RARα-knockin mice. These findings imply that upregulation of cyclin A1 is not essential for leukemogenesis. Our data suggest that cyclin A1 does not represent a suitable target for AML therapy.
authors.affiliation: Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Bäumer
authors.affiliation: Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bäumer
authors.affiliation: Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany; Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
authors.forename: Miriam
authors.initials: M
authors.lastname: Haak
authors.affiliation: Department of Medicine (Hematology, Oncology, Hemostaseology, and SCT), Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Koschmieder
authors.affiliation: Central Institute of Mental Health, Department of Molecular Biology, Heidelberg University, Mannheim, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Schönig
authors.affiliation: Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Berdel
authors.affiliation: Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany; Dept. of Medicine IV, Hematology and Oncology, University of Halle, Halle, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Müller-Tidow
mesh_terms: D000818:Animals; D056750:Cyclin A1 / Q000235:genetics*; D015973:Gene Expression Regulation, Leukemic; D055879:Gene Knock-In Techniques; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015854:Up-Regulation
chemical_list: D056750:Cyclin A1; D015514:Oncogene Proteins, Fusion; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein