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Nat Med. 1999 Nov;5(11):1277-84.

CD47 ligation induces caspase-independent cell death in chronic lymphocytic leukemia.

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1
Laboratoire d'allergie, Centre de Recherche du Centre Hospitalier de l' Université de Montréal, Hôpital Notre-Dame, 1560 rue Sherbrooke Est, Université de Montréal H2L 4M1, Quebec, Canada.

Abstract

Thrombospondin forms a 'molecular bridge' between phagocytic and apoptotic cells through interaction with alphavbeta3/CD36. We report here that engagement of CD47, a newly described thrombospondin receptor, by immobilized monoclonal antibody against CD47 or by thrombospondin induced in all B-cell chronic lymphocytic leukemia clones the cytoplasmic features of apoptosis (cell shrinkage, decrease in mitochondrial transmembrane potential and phosphatidylserine externalization) without the nuclear features (chromatin condensation, appearance of single-stranded DNA, DNA fragmentation and cleavage of poly ADP-ribose polymerase). These cytoplasmic events of apoptosis were not prevented by the addition of caspase inhibitor z-VAD-fmk, or by the presence of survival factors (such as interleukin-4 and gamma interferon) or cell activation. Morphological studies confirmed the integrity of the nucleus and showed swelling of the mitochondria. This caspase-independent death pathway may be relevant to the development of alternate therapeutic strategies in chronic lymphocytic leukemia, which remains an incurable disease.

PMID:
10545994
DOI:
10.1038/15233
[Indexed for MEDLINE]

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