TY - JOUR
T1 - CD38 and CD100 lead a network of surface receptors relaying positive signals for B-CLL growth and survival
AU - Deaglio, Silvia
AU - Vaisitti, Tiziana
AU - Bergui, Luciana
AU - Bonello, Lisa
AU - Horenstein, Alberto L.
AU - Tamagnone, Luca
AU - Boumsell, Laurence
AU - Malavasi, Fabio
PY - 2005
Y1 - 2005
N2 - This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/ CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/ CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir. © 2005 by The American Society of Hematology.
AB - This work addresses the question whether CD38, a negative prognostic marker in B-cell chronic lymphocytic leukemia (B-CLL), plays a role in neoplastic B-cell growth and survival. We show that CD38+ B-CLL cells bind to murine fibroblasts transfected with the CD31 ligand. The interaction triggers an extensive remodeling of the B-CLL membrane, with relocalization of BCR/CD19 to the CD38/CD31 contact areas, and it also increases cell survival and proliferation. A second event is the up-modulation of the survival receptor CD100, restricted to proliferating cells, and a concomitant decrease of CD72 (low-affinity CD100 ligand and negative regulator of immune responses). The most efficient signals are delivered through sequential interactions between CD38/ CD31 and CD100/plexin-B1 (high-affinity CD100 ligand), as inferred by coculture experiments using specific transfectants and blocking monoclonal antibodies (mAbs). The finding that nurselike cells from B-CLL patients express CD31 and plexin-B1, which deliver growth and survival signals to CD38+/ CD100+ B-CLL cells, further confirms the model proposed. These findings show that a set of normal receptors and ligands ruling physiologic signaling pathways in B lymphocytes becomes detrimental when expressed in the context of B-CLL cells, ultimately leading to the generation of a tumor reservoir. © 2005 by The American Society of Hematology.
KW - B-CLL
KW - CD100
KW - CD38
KW - LYMPHOCYTIC LEUKEMIA
KW - B-CLL
KW - CD100
KW - CD38
KW - LYMPHOCYTIC LEUKEMIA
UR - http://hdl.handle.net/10807/141008
U2 - 10.1182/blood-2004-10-3873
DO - 10.1182/blood-2004-10-3873
M3 - Article
SN - 0006-4971
VL - 105
SP - 3042
EP - 3050
JO - Blood
JF - Blood
ER -