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Blood, Vol. 92 No. 3 (August 1), 1998:
pp. 1031-1043
B-Cell Chronic Lymphocytic Leukemia Cells Express a Functional
Inducible Nitric Oxide Synthase Displaying Anti-Apoptotic Activity
Haixia Zhao,
Nathalie Dugas,
Claire Mathiot,
Alain Delmer,
Bernard Dugas,
François Sigaux, and
Jean-Pierre Kolb
From INSERM U365 and Service d'Hématologie, Institut Curie,
Paris; Laboratoire virus, neurone et immunité, UFR Kremlin
Bicêtre, Kremlin Bicêtre, Service d'Hématologie,
Hôpital de l'Hôtel Dieu, Paris; Fractales Biotech,
Hôpital Saint Joseph, Paris; and INSERM U462, Hôpital Saint
Louis, Paris.
The expression of different isoforms of nitric oxide synthase (NOS)
was investigated in B-cell chronic lymphocytic leukemia (B-CLL) to
delineate a possible role for nitric oxide (NO) in the control of
apoptosis of the tumoral cells. By reverse transcription-polymerase chain reaction (RT-PCR), all B-CLL cells were found to express spontaneously inducible NOS (iNOS) mRNA, whereas endothelial
constitutive NOS (ecNOS) mRNA was undetectable. The iNOS protein was
detected by immunofluorescence in the cytoplasm of permeabilized
leukemic cells and identified by Western blotting, using different
anti-iNOS antibodies, as a protein of 135 kD in B-CLL
cytoplasmic extracts. B-CLL cell lysates also displayed basal NOS
enzymatic activity, as measured by the conversion of
14C-labeled L-arginine into 14C-L-citrulline.
Ligation of CD23, expressed on the vast majority of B-CLL cells,
resulted in increased iNOS expression and activity. The NO released
exerted an anti-apoptotic effect on B-CLL cells that was counteracted
by NOS inhibitors and engagement of the APO-1/Fas pathway. Therefore,
the existence of a functional iNOS in B-CLL cells will provide further
insights into the mechanisms that control proliferation and apoptosis
in these tumor cells.
© 1998 by The American Society of Hematology.

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