title: Differential expression of aurora-A kinase in T-cell lymphomas.
abstract: 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.
authors: Department of Pathology and Laboratory Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
authors: Rashmi
authors: R
authors: Kanagal-Shamanna
authors: Norman L
authors: NL
authors: Lehman
authors: James P
authors: JP
authors: O'Donnell
authors: Megan S
authors: MS
authors: Lim
authors: Daniel S
authors: DS
authors: Schultz
authors: Dhananjay A
authors: DA
authors: Chitale
authors: Carlos E
authors: CE
authors: Bueso-Ramos
authors: L Jeffrey
authors: LJ
authors: Medeiros
authors: Kedar V
authors: KV
authors: Inamdar
mesh_terms: D064096:Aurora Kinase A / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D016399:Lymphoma, T-Cell / Q000201:enzymology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D064096:Aurora Kinase A