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Centrosome aberrations – hen or egg in cancer initiation and progression?

Leukemia volume 19, pages 1142–1144 (2005)Cite this article

In the current issue of Leukemia, Giehl et al1 describe the presence of centrosome aberrations in chronic myeloid leukemia (CML) cells. As such, this finding does not come as a surprise. Centrosomal abnormalities have been described in the vast majority of solid tumors2, 3, 4, 5, 6, 7, 8, 9, 10, 11 as well as in all hematological malignancies examined to date, including acute myeloid leukemia, Hodgkin's and non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and multiple myeloma.12, 13, 14, 15, 16, 17, 18, 19, 20

As the primary microtubule organizing center of eukaryotic cells, the centrosome functions as the site for the nucleation of microtubules and thereby plays a fundamental role in organizing the interphase cytoskeleton and the mitotic spindle function that is essential for accurate chromosome segregation.21 Centrosomes duplicate precisely once per cell cycle, thereby ensuring a strictly bipolar mitotic spindle axis.22 Replication of centrosomes is initiated at the G1/S transition of the cell cycle and dependent on phosphorylation of the retinoblastoma (Rb) protein, subsequent transcriptional activity of E2F, and activation of cyclin-dependent kinase (cdk) 2.23, 24, 25 Apart from deregulation of components of the Rb pathway, which occurs in almost all human neoplasias, several other proteins have been implicated in the centrosome amplification process, including loss or mutational inactivation of p53.26 It has long been recognized that errors in centrosome replication will lead to the formation of monopolar or multipolar mitoses, which, in turn, might be a cause of chromosomal instability and thus contribute to malignant transformation or cancer progression.

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  1. Medizinische Klinik V, Universität Heidelberg, Heidelberg, Germany

    A Krämer

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Krämer, A. Centrosome aberrations – hen or egg in cancer initiation and progression?. Leukemia 19, 1142–1144 (2005). https://doi.org/10.1038/sj.leu.2403780

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