Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival
Aberrant expression of B-lymphocyte stimulator by B chronic lymphocytic leukemia cells: a mechanism for survival
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DOI：
10.1182/blood-2002-02-0558
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发表时间：
2002-10-15
期刊：
影响因子：
20.3
通讯作者：
Jelinek, DF
中科院分区：
文献类型：
--
作者：
Novak, AJ;Bram, RJ;Jelinek, DF
B细胞慢性淋巴细胞白血病（B-CLL）的定义是外周和骨髓中CD 5（+）B细胞的积聚。这种疾病的特征不是高度增殖的细胞，而是存在对细胞凋亡具有显著抗性的白血病细胞，因此，存活期延长。B淋巴细胞刺激因子（B-lymphocyte stimulator，BLyS）是新近发现的一种肿瘤坏死因子（tumor necrosis factor，TNF）家族成员，与另一个TNF超家族成员APRIL具有重要的同源性。BLyS对正常B细胞维持和存活的显著作用提高了它可能参与血液恶性肿瘤（包括B-CLL）的发病机制和维持的可能性。在这项研究中，我们研究了APRIL和BLyS表达的状态，以及它们的受体，在这种疾病中。研究的所有B-CLL患者细胞表达BLyS的3种已知受体中的一种或多种;然而，表达模式是可变的。此外，我们首次证明，B-CLL细胞从一个子集的患者异常表达BLyS和APRIL mRNA，而这些分子在正常的B细胞检测不到。此外，我们提供了体外证据表明BLyS保护B-CLL细胞免于凋亡并提高细胞存活率。由于这些分子是B细胞稳态和肿瘤进展的关键调节因子，因此白血病细胞自分泌表达BLyS和APRIL可能在该疾病的发病机制中起重要作用。
B-cell chronic lymphocytic leukemia (B-CLL) is defined by the accumulation of CD5(+) B cells in the periphery and bone marrow. This disease is not characterized by highly proliferative cells but rather by the presence of leukemic cells with significant resistance to apoptosis and, therefore, prolonged survival. B-lymphocyte stimulator (BLyS) is a newly identified tumor necrosis factor (TNF) family member shown to be critical for maintenance of normal B-cell development and homeostasis and it shares significant homology with another TNF superfamily member, APRIL. The striking effects of BLyS on normal B-cell maintenance and survival raises the possibility that it may be involved in pathogenesis and maintenance of hematologic malignancies, including B-CLL. In this study, we investigated the status of APRIL and BLyS expression, as well as their receptors, in this disease. All B-CLL patient cells studied expressed one or more of 3 known receptors for BLyS; however, the pattern of expression was variable. In addition, We demonstrate for the first time that B-CLL cells from a subset of patients aberrantly express BLyS and APRIL mRNA, whereas these molecules were not detectable in normal B cells. Furthermore, we provide in vitro evidence that BLyS protects B-CLL cells from apoptosis and enhances cell survival. Because these molecules are key regulators of B-cell homeostasis and tumor progression, leukemic cell autocrine expression of BLyS and APRIL may be playing an important role in the pathogenesis of this disease.