CD38 expression in chronic lymphocytic leukemia is regulated by the tumor microenvironment
- 15 May 2008
- journal article
- Published by American Society of Hematology in Blood
- Vol. 111 (10), 5173-5181
- https://doi.org/10.1182/blood-2007-08-108605
Abstract
Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with a highly variable outcome. The prognosis of patients with CLL may be predicted using a number of biomarkers, including the level of CD38 expression at the leukemic cell surface. This study investigates the hypothesis that CD38 expression by CLL cells reflects interactions with nonmalignant cells within pseudofollicles in secondary lymphoid tissue where tumor cell proliferation is thought to occur. CD38 expression is higher in tissues that contain pseudofollicles compared with those that do not. In addition, we show that CD38 expression in CLL is dynamic, changes in response to contact with activated CD4+ T cells, and identifies cells that are primed to proliferate. Finally, we demonstrate close contact between activated CD4+ T cells and proliferating tumor in primary patient tissue. Proliferating tumor cells in lymph nodes express CD38, which is in turn associated with an increased number of CD31+ vascular endothelial cells. Although the factors resulting in colocalization of tumor, T cells, and endothelium remain unclear, the existence of these cellular clusters may provide an explanation for the association between CD38 expression and adverse outcome in CLL and suggests novel therapeutic targets.Keywords
This publication has 39 references indexed in Scilit:
- CD38 and ZAP-70 are functionally linked and mark CLL cells with high migratory potentialBlood, 2007
- CD38 expression labels an activated subset within chronic lymphocytic leukemia clones enriched in proliferating B cellsBlood, 2007
- B‐cell chronic lymphocytic leukaemia cells show specific changes in membrane protein expression during different stages of cell cycleBritish Journal of Haematology, 2007
- CD38 expression levels in chronic lymphocytic leukemia B cells are associated with activation marker expression and differential responses to interferon stimulationLeukemia, 2005
- CLL, but not normal, B cells are dependent on autocrine VEGF and α4β1 integrin for chemokine-induced motility on and through endotheliumBlood, 2005
- CD38 expression on B-cell chronic lymphocytic leukemic cells is strongly correlated with vascular endothelial growth factor expressionLeukemia, 2004
- CD100/Plexin-B1 interactions sustain proliferation and survival of normal and leukemic CD5+ B lymphocytesBlood, 2003
- The pattern of CD38 expression defines a distinct subset of chronic lymphocytic leukemia (CLL) patients at risk of disease progressionBlood, 2003
- The human immunoglobulin VH repertoireImmunology Today, 1995
- CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cellsEuropean Journal of Immunology, 1994