CD38/CD31 interactions activate genetic pathways leading to proliferation and migration in chronic lymphocytic leukemia cells.
Human CD38 is a pleiotropic glycoprotein belonging to a family of enzymes/receptors involved in the catabolism of extracellular nucleotides. CD38-receptor activities are regulated through binding to the nonsubstrate ligand CD31. CD38 expression above a critical threshold is a negative prognostic marker for chronic lymphocytic leukemia (CLL) patients. Activation of CD38 by means of agonistic monoclonal antibodies or the CD31 ligand induces proliferation and immunoblast differentiation of CLL cells. Here we define the genetic signature that follows long-term in vitro interactions between CD38(+) CLL lymphocytes and CD31(+) cells. The emerging profile confirms that the CD31/CD38 axis activates genetic programs relevant for proliferative responses. It also indicates a contribution of this pathway to the processes mediating migration and homing. These results further support the notion that the CD31/CD38 axis is part of a network of accessory signals that modify the microenvironment, favoring localization of leukemic cells to growth-permissive sites.
Deaglio
Silvia
S
Department of Genetics, Biology and Biochemistry, of Torino Medical School, Turin, Italy. silvia.deaglio@unito.it
Aydin
Semra
S
Grand
Maurizia Mello
MM
Vaisitti
Tiziana
T
Bergui
Luciana
L
D'Arena
Giovanni
G
Chiorino
Giovanna
G
Malavasi
Fabio
F
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000818:Animals; D048708:Cell Growth Processes / Q000235:genetics; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051997:ADP-ribosyl Cyclase 1