Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia
Expression and prognostic significance of the inhibitor of apoptosis protein (IAP) family and its antagonists in chronic lymphocytic leukaemia
复制标题
DOI：
10.1016/j.ejca.2009.11.023
复制
发表时间：
2010-03-01
影响因子：
8.4
通讯作者：
Smolewski, Piotr
中科院分区：
文献类型：
--
作者：
Grzybowska-Izydorczyk, Olga;Cebula, Barbara;Smolewski, Piotr
细胞凋亡受损仍然被认为是慢性淋巴细胞白血病（CLL）发生和发展的重要事件。然而，这种缺陷的机制尚未完全阐明。在这项研究中，凋亡抑制蛋白，IAP的表达，（cIAP 1、cIAP 2、XIAP和存活素）及其拮抗剂（Smac/DIABLO和HtrA2/Omi）在100例未经治疗的CLL患者中进行综合分析，流式细胞术和Western blot技术显示，白血病细胞中抗凋亡cIAP 1和cIAP 2的表达显著高于非肿瘤淋巴细胞（分别为p = 0.000001和p = 0.014），而IAP拮抗剂Smac/DIABLO在CLL中降低（p = 0.010）。与稳定CLL患者相比，在疾病进展患者中发现所有分析的IAP（cIAP 1，p = 0.002; cIAP 2，p = 0.026; XIAP，p = 0.002;生存素，p = 0.00006）表达更高，Smac/DIABLO水平更低（p = 0.006）。cIAP1和生存素的高基线表达与对治疗的不良反应相关。这些蛋白质的共表达与CLL患者的总生存期较短相关（p = 0.005）。总之，CLL细胞显示出IAP/IAP拮抗剂表达的抗凋亡特征。IAP的上调与疾病的进展过程相关。clAP 1和生存素的共表达似乎是CLL患者的不利预后因素。需要更长时间随访的进一步研究来证实和扩展这些发现。(C)2009爱思唯尔有限公司保留所有权利。
Impaired apoptosis is still considered to be an important event in the development and progression of chronic lymphocytic leukaemia (CLL). However, mechanisms of this defect have not been fully elucidated. In this study, expression of inhibitor of apoptosis proteins, IAPs (cIAP1, cIAP2, XIAP and survivin), and their antagonists (Smac/DIABLO and HtrA2/Omi) was comprehensively analysed in 100 untreated CLL patients, using flow cytometry and Western blot techniques.Expression of anti-apoptotic cIAP1 and cIAP2 in leukaemic cells was significantly higher than in non-tumour lymphocytes (p = 0.000001 and p = 0.014, respectively), whereas the IAP-antagonist, Smac/DIABLO, was decreased in CLL (p = 0.010). Higher expression of all analysed IAPs (cIAP1, p = 0.002; cIAP2, p = 0.026; XIAP, p = 0.002; survivin, p = 0.00006) and lower levels of Smac/DIABLO (p = 0.006) were found in patients with progressive disease, compared to those with stable CLL. High baseline expression of cIAP1 and survivin correlated with worse response to treatment. Co-expression of these proteins was associated with shorter overall survival of CLL patients (p = 0.005).In conclusion, CLL cells show the apoptosis-resistant profile of IAPs/IAP-antagonist expression. Upregulation of IAPs is associated with a progressive course of the disease. Co-expression of clAP1 and survivin seems to be an unfavourable prognostic factor in CLL patients. Further studies with longer follow up are warranted to confirm and expand these findings. (C) 2009 Elsevier Ltd. All rights reserved.