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

Javeed Iqbal, D. D. Weisenburger, A. Chowdhury, M. Y. Tsai, G. Srivastava, Timothy Charles Greiner, C. Kucuk, K. Deffenbacher, Julie Marie Vose, Lynette M Smith, W. Y. Au, S. Nakamura, M. Seto, J. Delabie, F. Berger, F. Loong, Y. H. Ko, I. Sng, X. Liu, T. P. LoughranJames Olen Armitage, W. C. Chan

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96 Scopus citations

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 γ-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These γ-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 γ T cells. They showed distinct expression of Vγ9, V2 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.

Original languageEnglish (US)
Pages (from-to)348-358
Number of pages11
JournalLeukemia
Volume25
Issue number2
DOIs
StatePublished - Feb 2011

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Keywords

  • NOTCH pathway
  • aurora kinase A
  • gene-expression signature

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Iqbal, J., Weisenburger, D. D., Chowdhury, A., Tsai, M. Y., Srivastava, G., Greiner, T. C., Kucuk, C., Deffenbacher, K., Vose, J. M., Smith, L. M., Au, W. Y., Nakamura, S., Seto, M., Delabie, J., Berger, F., Loong, F., Ko, Y. H., Sng, I., Liu, X., ... Chan, W. C. (2011). 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(2), 348-358. https://doi.org/10.1038/leu.2010.255