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Differential expression of aurora-A kinase in T-cell lymphomas

2013; Elsevier BV; Volume: 26; Issue: 5 Linguagem: Inglês

10.1038/modpathol.2012.211

1530-0285

Rashmi Kanagal‐Shamanna, Norman L. Lehman, James P. O’Donnell, Megan S. Lim, Daniel Schultz, Dhananjay Chitale, Carlos E. Bueso‐Ramos, L. Jeffrey Medeiros, Kedar Inamdar,

Neuroblastoma Research and Treatments

Aurora-A is a mitotic kinase implicated in oncogenesis and is known to be overexpressed in B-cell lymphomas and plasma cell myeloma. The expression of Aurora-A kinase (henceforth referred to as Aurora-A) in T-cell lymphomas is not well characterized. In this study, we assessed Aurora-A expression by immunohistochemical analysis in 100 lymphomas encompassing a variety of T-cell lymphomas as categorized in the World Health Organization classification. Aurora-A expression was highest in anaplastic large-cell lymphomas and variably expressed in other types of T-cell lymphomas. In addition, the pattern of Aurora-A expression was predominantly cytoplasmic in ALK-positive anaplastic large-cell lymphoma and was nuclear in ALK-negative anaplastic large-cell lymphoma and other T-cell lymphomas, suggesting altered biochemical mechanisms of Aurora-A nuclear transport in ALK-positive anaplastic large-cell lymphoma. Reverse transcriptase-PCR analysis showed that Aurora-A is more highly expressed in ALK-positive anaplastic large-cell lymphoma than in ALK-negative anaplastic large-cell lymphoma, and is relatively lower in peripheral T-cell lymphomas. Using western blot analysis and the DEL cell line (derived from ALK-positive anaplastic large-cell lymphoma), we showed that Aurora-A expression is decreased after treatment with either MYC or MEK inhibitors, consistent with the MYC and MAP kinase signaling pathways being involved in driving Aurora-A expression; the greatest decrease was observed after MYC inhibition. These findings provide insights into the possible importance of Aurora-A overexpression in anaplastic large-cell lymphoma pathogenesis, and also suggest that Aurora-A inhibition could be a potential therapeutic approach for patients with anaplastic large-cell lymphoma.