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

Nat Med. 1999 Nov;5(11):1277-84. doi: 10.1038/15233.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / immunology*
  • Apoptosis / immunology
  • CD47 Antigen
  • Carrier Proteins / immunology*
  • Caspases / metabolism*
  • Flow Cytometry
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / enzymology
  • Leukemia, Lymphocytic, Chronic, B-Cell / immunology
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology*
  • Middle Aged


  • Antigens, CD
  • CD47 Antigen
  • CD47 protein, human
  • Carrier Proteins
  • Caspases