Survivin is expressed on CD40 stimulation and interfaces proliferation andapoptosis in B-cell chronic lymphocytic leukemia

In B-cell chronic lymphocytic leukemia (B-CLL), defective apoptosis causes the accumulation of mature CD5(+) B cells in lymphoid organs, bone marrow ( BM), and peripheral blood (PB). These cells are the progeny of a proliferat ing pool that feeds the accumulating compartment. The authors sought to det ermine which molecular mechanisms govern the proliferating pool, how they r elate to apoptosis, and what the role is of the microenvironment. To begin to resolve these problems, the expression and modulation of the family of i nhibitor of apoptosis proteins (IAPs) were investigated, with consideration given to the possibility that physiological stimuli, such as CD40 ligand ( CD40L), available to B cells in the microenvironment, might modulate IAP ex pression. The in vitro data on mononuclear cells from PB or BM of 30 patien ts demonstrate that B-CLL cells on CD40 stimulation express Survivin and th at Survivin is the only IAP whose expression is induced by CD40L. Through i mmunohistochemistry, in vivo Survivin expression in lymph node (LN) and BM biopsies was evaluated. In reactive LN, Survivin was detected only in highl y proliferating germinal center cells. In LN from patients with B-CLL. Surv ivin was detected only in pseudofollicles. Pseudofollicle Survivin(+) cells were actively proliferating and, in contrast to Survivin+ B cells found in normal GC, were Bcl-2(+). In B-CLL BM biopsies, CD5(+), Survivin+ cells we re observed in clusters interspersed with T cells. These findings establish that Survivin controls the B-CLL proliferative pool interfacing apoptosis and that its expression may be modulated by microenvironmental stimuli. (Bl ood. 2001;97:2777-2783) (C) 2001 by The American Society of Hematology.