Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia
Survivin is expressed on CD40 stimulation and interfaces proliferation and apoptosis in B-cell chronic lymphocytic leukemia
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DOI：
10.1182/blood.v97.9.2777
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发表时间：
2001-05-01
期刊：
影响因子：
20.3
通讯作者：
Caligaris-Cappio, F
中科院分区：
文献类型：
--
作者：
Granziero, L;Ghia, P;Caligaris-Cappio, F
在B细胞慢性淋巴细胞白血病（B-CLL）中，缺陷性凋亡导致成熟的CD 5（+）B细胞在淋巴器官、骨髓（BM）和外周血（PB）中积累。这些细胞是增殖池的后代，增殖池为积累室提供营养。作者试图确定哪些分子机制控制增殖池，它们如何与凋亡相关，以及微环境的作用是什么。为了开始解决这些问题，研究了凋亡抑制蛋白（IAP）家族的表达和调节，考虑了微环境中B细胞可获得的生理刺激物如CD 40配体（CD 40 L）可能调节IAP表达的可能性。对30例患者外周血或骨髓单个核细胞的体外数据表明，CD 40刺激的B-CLL细胞表达Survivin，Survivin是唯一由CD 40 L诱导表达的IAP。通过免疫组化，在体内生存素在淋巴结（LN）和骨髓活检的表达进行了评价。在反应性LN中，仅在高度增殖的生发中心细胞中检测到Survivin。在B-CLL患者的LN中。Survivin仅在假卵泡中表达。假滤泡Survivin（+）细胞增殖活跃，与正常GC中Survivin+ B细胞不同，假滤泡Survivin（+）细胞为Bcl-2（+）。在B-CLL BM活检中，观察到CD 5（+）、Survivin+细胞成簇散布于T细胞中。这些研究结果表明，Survivin控制B-CLL增殖池介导的凋亡，其表达可能受到微环境刺激的调节。（血。2001;97：2777-2783）（C）2001由美国血液学学会。
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 proliferating pool that feeds the accumulating compartment. The authors sought to determine which molecular mechanisms govern the proliferating pool, how they relate to apoptosis, and what the role is of the microenvironment. To begin to resolve these problems, the expression and modulation of the family of inhibitor 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 expression. The in vitro data on mononuclear cells from PB or BM of 30 patients demonstrate that B-CLL cells on CD40 stimulation express Survivin and that Survivin is the only IAP whose expression is induced by CD40L. Through immunohistochemistry, in vivo Survivin expression in lymph node (LN) and BM biopsies was evaluated. In reactive LN, Survivin was detected only in highly proliferating germinal center cells. In LN from patients with B-CLL. Survivin 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 were 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. (Blood. 2001;97:2777-2783) (C) 2001 by The American Society of Hematology.