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Selective apoptosis of natural killer-cell tumours by l-asparaginase.

Authors :
Ando M
Sugimoto K
Kitoh T
Sasaki M
Mukai K
Ando J
Egashira M
Schuster SM
Oshimi K
Source :
British journal of haematology [Br J Haematol] 2005 Sep; Vol. 130 (6), pp. 860-8.
Publication Year :
2005

Abstract

We examined the effectiveness of various anti-tumour agents to natural killer (NK)-cell tumour cell lines and samples, which are generally resistant to chemotherapy, using flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Although NK-YS and NK-92 were highly resistant to various anti-tumour agents, l-asparaginase induced apoptosis in these two NK-cell lines. NK-cell leukaemia/lymphoma and acute lymphoblastic leukaemia (ALL) samples were selectively sensitive to l-asparaginase and to doxorubicin (DXR) respectively. Samples of chronic NK lymphocytosis, an NK-cell disorder with an indolent clinical course, were resistant to both drugs. Our study clearly separated two major categories of NK-cell disorders and ALL according to the sensitivity to DXR and l-asparaginase. We examined asparagine synthetase levels by real-time quantitative polymerase chain reaction (RQ-PCR) and immunostaining in these samples. At least in nasal-type NK-cell lymphoma, there was a good correlation among asparagine synthetase expression, in vitro sensitivity and clinical response to l-asparaginase. In aggressive NK-cell leukaemia, although asparagine synthetase expression was high at both mRNA and protein levels, l-asparaginase induced considerable apoptosis. Furthermore, samples of each disease entity occupied a distinct area in two-dimensional plotting with asparagine synthetase mRNA level (RQ-PCR) and in vitrol-asparaginase sensitivity (TUNEL assay). We confirmed rather specific anti-tumour activity of l-asparaginase against NK-cell tumours in vitro, which provides an experimental background to the clinical use of l-asparaginase for NK-cell tumours.

Details

Language :
English
ISSN :
0007-1048
Volume :
130
Issue :
6
Database :
MEDLINE
Journal :
British journal of haematology
Publication Type :
Academic Journal
Accession number :
16156856
Full Text :
https://doi.org/10.1111/j.1365-2141.2005.05694.x