Targeting the microenvironment in chronic lymphocytic leukemia offers novel therapeutic options.
Chronic lymphocytic leukemia (CLL) cells display features consistent with a defect in apoptosis and exhibit prolonged survival in vivo. Survival of these malignant cells is influenced by interactions with non-leukemic cells located in permissive niches in lymphoid organs. Leukemic cells subvert the normal architecture of the lymphoid organs, recruiting stromal cells, dendritic cells and T lymphocytes, all reported as playing active roles in the survival and proliferation of CLL. The same survival-promoting environment also rescues/protects leukemic cells from cytotoxic therapies, giving way to disease relapse. This review summarizes and discusses current knowledge about the intricate network of soluble and cell-bound signals regulating the life and death of CLL cells in different districts. At the same time, it seeks to hone in on which discrete molecular elements are best suited as targets for treating this still incurable disease.
Department of Medical Sciences, University of Turin, School of Medicine, Turin, Italy; Human Genetics Foundation (HuGeF), Turin, Italy.
Valentina
V
Audrito
Tiziana
T
Vaisitti
Sara
S
Serra
Cinzia
C
Bologna
Davide
D
Brusa
Fabio
F
Malavasi
Silvia
S
Deaglio
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects
D000970:Antineoplastic Agents