A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis

Nicole Bäumer; Sebastian Bäumer; Miriam Haak; Steffen Koschmieder; Kai Schönig; Wolfgang E Berdel; Carsten Müller-Tidow

doi:10.1371/journal.pone.0129147

A Limited Role for the Cell Cycle Regulator Cyclin A1 in Murine Leukemogenesis

PLoS One. 2015 Jun 16;10(6):e0129147. doi: 10.1371/journal.pone.0129147. eCollection 2015.

Authors

Nicole Bäumer¹, Sebastian Bäumer¹, Miriam Haak², Steffen Koschmieder³, Kai Schönig⁴, Wolfgang E Berdel¹, Carsten Müller-Tidow⁵

Affiliations

¹ Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
² Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany; Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
³ Department of Medicine (Hematology, Oncology, Hemostaseology, and SCT), Faculty of Medicine, RWTH Aachen University, Aachen, Germany.
⁴ Central Institute of Mental Health, Department of Molecular Biology, Heidelberg University, Mannheim, Germany.
⁵ Department of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany; Dept. of Medicine IV, Hematology and Oncology, University of Halle, Halle, Germany.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cyclin A1 / genetics*
Gene Expression Regulation, Leukemic
Gene Knock-In Techniques
Leukemia, Myeloid, Acute / genetics*
Leukemia, Myeloid, Acute / pathology*
Mice
Mice, Knockout
Mice, Transgenic
Oncogene Proteins, Fusion / genetics
Up-Regulation

Substances

Cyclin A1
Oncogene Proteins, Fusion
promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein

Grants and funding

This study was supported by grants from the Deutsche Forschungsgemeinschaft (Mu 1328/2-3; www.dfg.de) and the Deutsche Krebshilfe (10-1539-Mü3; www.krebshilfe.de). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Miltenyi Biotec GmbH provided support in the form of salary for author "MH," but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the "author contributions" section.