Gene expression patterns in acute myeloid leukemia correlate with centrosome aberrations and numerical chromosome changes
- 9 February 2004
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 23 (13), 2379-2384
- https://doi.org/10.1038/sj.onc.1207401
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.Keywords
This publication has 27 references indexed in Scilit:
- Gene Expression Patterns in Ependymomas Correlate with Tumor Location, Grade, and Patient AgeThe American Journal of Pathology, 2003
- Genome‐wide analysis of acute myeloid leukemia with normal karyotype reveals a unique pattern of homeobox gene expression distinct from those with translocation‐mediated fusion eventsGenes, Chromosomes and Cancer, 2003
- Overexpression of Cdk6–cyclin D3 highly sensitizes cells to physical and chemical transformationOncogene, 2003
- Centrosome aberrations in acute myeloid leukemia are correlated with cytogenetic risk profileBlood, 2003
- Centrosome replication, genomic instability and cancerLeukemia, 2002
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001
- Requirement of Cdk2-Cyclin E Activity for Repeated Centrosome Reproduction in Xenopus Egg ExtractsScience, 1999
- Pericentrin and γ-Tubulin Form a Protein Complex and Are Organized into a Novel Lattice at the CentrosomeThe Journal of cell biology, 1998
- How Cells Get the Right ChromosomesScience, 1997
- Pathways of spindle assemblyCurrent Opinion in Cell Biology, 1997