NK-Cell Lymphoma Shares Strikingly Similar Molecular Features with a Distinct Set of γδ T-Cell Lymphoma and Identification of Aurora Kinase A Inhibitor as a Novel Therapeutic Agent

• Published in: Blood 2009-11, Vol.114 (22), p.313-313
• Main Authors: Iqbal, Javeed, Weisenburger, Dennis D., Chowdhury, Aparajita, Srivastava, Gopesh, Greiner, Timothy C., Deffenbacher, Karen E, Kucuk, Can, Vose, Julie M., Au, Wing, Nakamura, Shigeo, Seto, Masao, Delabie, Jan, Berger, Francoise, Loong, Florence, Ko, Young-Hyeh, Sng, Ivy, Liu, Xin, Loughran, Thomas P., Tsai, Ming, Armitage, James O., Chan, Wing C.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V114.22.313.313

Abstract 313 Natural Killer (NK) cell lymphomas (NKCL) are rare with aggressive clinical behavior. The majority of these cases belong to extra-nodal NK/T-cell lymphoma of nasal type (ENKTL) of the current World Health Organization (WHO) classification scheme. ENKTL also includes peripheral T-cell lymphomas (PTCL) that are similar in many respects to the NK cell counterpart. Due to rarity of the disease and difficulty in obtaining adequate biopsy specimens, the molecular mechanisms underlining ENKTL are largely unknown. We profiled a series of NK-cell lymphoma cases and many well- characterized cell lines of NK- and T-cell lineages to define molecular classifiers that can distinguish NKCL from PTCL, including lymphomas of cytotoxic T-cells. We also evaluated oncogenic pathways in these tumors and the therapeutic potential of a novel inhibitor of a cell cycle regulator (aurora kinase A). The gene expression profiling (GEP) of ENKTL (n=21) and PTCL-U (n=50) cases were performed using HG U133 plus 2 arrays (Affymetrix Inc, CA). GEP of other PTCL subtypes (n=90), normal NK and T cells (resting and activated), NK and T cell lines (n=14) and indolent NK- cell/large granular lymphocytic proliferation (NK-LGLP) (n=5) were used for comparative analysis. Immunohistochemistry (IHC) was used to validate the GEP findings. A novel aurora-kinase-A inhibitor (MK-8745) was obtained from Merck & Co (Merck & Co., Inc. NJ, USA) and incubated with the cell lines for 2 -24 hours at 0.1-1 μM concentrations. The ENKTL showed a male predominance (2:1) with a median age of 55 years at diagnosis and aggressive clinical behavior [5-year OS (