No convincing evidence for a role of CD31-CD38 interactions in the pathogenesis of chronic lymphocytic leukemia.
Although CD38, a marker of poor prognosis in chronic lymphocytic leukemia (CLL), is known primarily as an ecto-enzyme, it has also been ascribed a receptor function. Interaction with its proposed ligand CD31 expressed on nurse-like cells would result in proliferative and survival-signals. Yet, in CLL, both homotypic and heterotypic CD31-CD38 interactions are expected to be rather ubiquitous. We analyzed whether CD38-CD31 interactions result in proliferative and antiapoptotic signals. We found a high expression of CD31 on CLL, irrespective of CD38 expression. Coculture of CD38(high) CLL with endothelial cells or CD31 transfected fibroblasts, with or without blocking CD31 or CD38 antibodies, did not result in increased survival or proliferation. Analysis of gene expression of most known regulators of apoptosis revealed no influence of coculture with CD31-expressing feeder cells. In conclusion, our data do not support an important contribution of CD38 triggering by CD31 to the proliferative and antiapoptotic state of the leukemic clone.
Tonino
Sanne H
SH
Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands. s.h.tonino@amc.uva.nl
Spijker
Rene
R
Luijks
Dieuwertje M P
DM
van Oers
Marinus H J
MH
Kater
Arnon P
AP
D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D049109:Cell Proliferation; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000209:etiology* / Q000473:pathology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism*; D011485:Protein Binding; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051997:ADP-ribosyl Cyclase 1