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Lymphoma

Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro

Leukemia volume 25, pages 348–358 (2011)Cite this article

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A Corrigendum to this article was published on 10 August 2011

Abstract

Natural killer (NK) cell lymphomas/leukemias are rare neoplasms with an aggressive clinical behavior. The majority of the cases belong to extranodal NK/T-cell lymphoma, nasal type (ENKTL) in the current WHO classification scheme. Gene-expression profiling (GEP) of 21 ENKTL and NK-cell lymphoma/leukemia patients, 17 NK- and T-cell lines and 5 indolent NK-cell large-granular-lymphocytic proliferation was performed and compared with 125 peripheral T-cell lymphoma (PTCL) patients previously studied. The molecular classifier derived for ENKTL patients was comprised of 84 transcripts with the majority of them contributed by the neoplastic NK cells. The classifier also identified a set of γδ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γδ-PTCLs expressed transcripts associated with the T-cell receptor (TCR)/CD3 complex, suggesting T cell rather than NK-cell lineage. They were very similar to NK-cell tumors by GEP, but were distinct from cytotoxic (αβ)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of γδ T cells. They showed distinct expression of Vγ9, Vδ2 transcripts and were positive for TCRγ, but negative for TCRβ by immunohistochemistry. Targeted inhibition of two oncogenic pathways (AURKA and NOTCH-1) by small-molecular inhibitors induced significant growth arrest in NK-cell lines, thus providing a rationale for clinical trials of these inhibitors in NK-cell malignancies.

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Acknowledgements

We thank Martin Bast for clinical data collection, and Kavita Patel and Lisa Bough for their technical assistance. This work was supported in part by NCI Grant 5U01/CA114778, Lymphoma SPORE P50CA136411-01(NC1) and funds from the International Peripheral T-cell Lymphoma Project and Eppley Cancer Institute Core Grant CA36727. The UNMC Microarray Core Facility is supported partially by NIH Grant P20 RR016469 from the INBRE Program of the National Center for Research Resources.

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Authors and Affiliations

  1. Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    J Iqbal, D D Weisenburger, T C Greiner, C Kucuk, K Deffenbacher & W C Chan

  2. Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA

    A Chowdhury & M Y Tsai

  3. Departments of Pathology and Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China

    G Srivastava, W Y Au & F Loong

  4. Division of Hematology and Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA

    J Vose & J Armitage

  5. College of Public Health, University of Nebraska Medical Center, Omaha, NE, USA

    L Smith

  6. Departments of Pathology and Cancer Genetics, Aichi Cancer Center Research Institute, Nagoya University, Nagoya, Japan

    S Nakamura & M Seto

  7. Department of Pathology, University of Oslo, Norwegian Radium Hospital, Oslo, Norway

    J Delabie

  8. Department of Pathology, Centre Hospitalier Lyon-Sud, Lyon, France

    F Berger

  9. Department of Pathology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea

    Y-H Ko

  10. Department of Pathology, Singapore General Hospital, Singapore

    I Sng

  11. Penn State Hershey Cancer Institute, Pennsylvania State University College of Medicine, Hershey, PA, USA

    X Liu & T P Loughran

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Presented in part at the oral-session at the 51st American Society of Hematology (ASH) Annual Meeting, New Orleans, LA, 5–8 December 2009.

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Iqbal, J., Weisenburger, D., Chowdhury, A. et al. Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro. Leukemia 25, 348–358 (2011). https://doi.org/10.1038/leu.2010.255

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