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Gene expression patterns in acute myeloid leukemia correlate with centrosome aberrations and numerical chromosome changes

Oncogene volume 23, pages 2379–2384 (2004)Cite this article

Abstract

Centrosomes, which mediate accurate chromosome segregation during mitosis, undergo duplication precisely once per cell division at the G1/S boundary. Recently, we described centrosome aberrations as a possible cause of aneuploidy in acute myeloid leukemia (AML) and found a correlation of the percentage of cells carrying abnormal centrosomes to their cytogenetic risk profile. To elucidate the molecular events responsible for the development of centrosome aberrations in AML, tumor RNA of 29 AML samples was hybridized to cDNA microarrays. The microarrays comprised some 2800 different genes with relevance to hematopoiesis, tumorigenesis and mitosis and included a set of 359 centrosome-associated genes. We identified two gene expression signatures, which allowed an accurate classification according to the extent of centrosome aberrations and the ploidy status in 28 of 29 patients each. Specifically, 18 genes were present in both signatures, including genes that code for cell cycle regulatory proteins (cyclin A2, cyclin D3, cyclin H, CDK6, p18INK4c, p21Cip1, PAK1) and centrosome-associated proteins (pericentrin, α2-tubulin, NUMA1, TUBGCP2, PRKAR2A). In conclusion, the high expression of centrosome-associated genes matches the description of centrosome aberrations in several tumor types. Moreover, in AML the identification of G1/S-phase stimulatory genes suggests that one mechanism of aneuploidy induction might be the deregulation of centrosome replication at the G1/S boundary.

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Acknowledgements

We thank Heidi Kramer and Brigitte Schreiter for their excellent technical assistance. This study was supported by two grants of the Bundesministerium für Bildung und Forschung (FKZ 01 KW 9937 and NGFN, 01 GR 0101). KN is a scholar of the Deutsche José Carreras Leukämie-Stiftung e.V (DJCLS 2001/NAT-3), AK is a Heisenberg scholar of the Deutsche Forschungsgemeinschaft.

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Authors and Affiliations

  1. Division of Molecular Genetics (B060), Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg, D-69120, Germany

    Kai Neben, Björn Tews, Gunnar Wrobel, Meinhard Hahn, Felix Kokocinski & Peter Lichter

  2. Medizinische Klinik und Poliklinik V, Universität Heidelberg, Hospitalstr. 3, Heidelberg, D-69115, Germany

    Kai Neben, Christian Giesecke, Ulf Krause, Anthony D Ho & Alwin Krämer

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  1. Kai Neben
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Correspondence to Peter Lichter.

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Neben, K., Tews, B., Wrobel, G. et al. Gene expression patterns in acute myeloid leukemia correlate with centrosome aberrations and numerical chromosome changes. Oncogene 23, 2379–2384 (2004). https://doi.org/10.1038/sj.onc.1207401

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