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

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Iqbal J., Weisenburger D. D., Chowdhury A., Tsai M. Y., Srivastava G., Greiner T. C., ...Daha Fazla

LEUKEMIA, cilt.25, sa.2, ss.348-358, 2011 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 2
  • Basım Tarihi: 2011
  • Doi Numarası: 10.1038/leu.2010.255
  • Dergi Adı: LEUKEMIA
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.348-358
  • Anahtar Kelimeler: NK-cell lymphoma, gamma delta T-cell lymphoma, molecular classifier, gene-expression signature, NOTCH pathway, aurora kinase A, GENE-EXPRESSION, ALPHA-BETA, A KINASE, NASAL, LEUKEMIA, LYMPHOCYTES, LINES, P53, NK, CLASSIFICATION
  • Dokuz Eylül Üniversitesi Adresli: Hayır

Özet

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 gamma delta-PTCLs both in the ENKTL cases as well as in cases initially classified as PTCL-not otherwise specified. These gamma delta-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 (alpha beta)-PTCL and hepatosplenic T-cell lymphoma, indicating derivation from an ontogenically and functionally distinct subset of gamma delta T cells. They showed distinct expression of V gamma 9, V delta 2 transcripts and were positive for TCR gamma, but negative for TCR beta by immuno-histochemistry. 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. Leukemia (2011) 25, 348-358; doi:10.1038/leu.2010.255; published online 5 November 2010