Grzybowska-Izydorczyk Olga, Smolewski Piotr
Katedra i Klinika Hematologii Uniwersytetu Medycznego w Łodzi.
Postepy Hig Med Dosw (Online). 2008 Feb 14;62:55-63.
The apoptotic mode of cell death is a major regulatory process in all complex organisms. The low proliferative index and slow accumulation of malignant cells in chronic lymphocytic leukemia (CLL), the most frequent type of leukemia in Europe and North America, suggests that the disease is caused by a defect in apoptosis regulation. Classical apoptosis is executed through the activation of caspases, cysteine proteases which are regulated by a number of pro- and anti-apoptotic proteins. One such checkpoint is the control of caspase activation by a relatively new family of inhibitor of apoptosis proteins (IAPs). They block both the mitochondrial-dependent and -independent apoptotic pathways. The IAP family inhibits apoptosis by binding to specific caspases and possibly by other mechanisms. They also participate in the regulation of cellular and intracellular signal transduction. Six human IAPs have been identified: XIAP, cIAP1, cIAP2, NAIP, livin, and survivin. Because of their important role in regulating apoptosis, IAPs are being investigated as a potential prognostic factor as well as a treatment target in cancer patients. Overexpression of several IAPs has been detected in various hematological malignancies, including acute leukemias, myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and many types of lymphoid malignancies, such as chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). Many publications revealed significant correlation between a high level of IAPs, especially of XIAP and survivin, and tumor progression. It seems that overexpression of XIAP in acute myeloid leukemia (AML) and survivin in acute lymphoblastic leukemia (ALL) and DLBCL could become a new unfavorable prognostic factor. Many studies are now concentrating on evaluating the expression and significance of the other proteins of the IAP family. In this paper the current knowledge of the importance of IAPs in hematological malignancies is presented.
细胞凋亡的死亡模式是所有复杂生物体中的一个主要调节过程。慢性淋巴细胞白血病（CLL）是欧洲和北美最常见的白血病类型，其恶性细胞增殖指数低且积累缓慢，这表明该疾病是由凋亡调节缺陷引起的。经典的细胞凋亡是通过半胱天冬酶（caspases）的激活来执行的，半胱天冬酶是一类受多种促凋亡蛋白和抗凋亡蛋白调节的半胱氨酸蛋白酶。其中一个这样的检查点是由一个相对较新的凋亡抑制蛋白（IAPs）家族对半胱天冬酶激活的控制。它们阻断线粒体依赖性和非依赖性凋亡途径。IAP家族通过与特定的半胱天冬酶结合以及可能的其他机制来抑制细胞凋亡。它们还参与细胞和细胞内信号转导的调节。已鉴定出六种人类IAP：XIAP、cIAP1、cIAP2、NAIP、livin和survivin。由于它们在调节细胞凋亡中的重要作用，IAPs正作为癌症患者潜在的预后因素以及治疗靶点进行研究。在各种血液系统恶性肿瘤中，包括急性白血病、骨髓增生异常综合征（MDS）、慢性粒细胞白血病（CML）以及许多类型的淋巴系统恶性肿瘤，如慢性淋巴细胞白血病（CLL）和弥漫性大B细胞淋巴瘤（DLBCL），都检测到了几种IAP的过表达。许多出版物揭示了高水平的IAP，尤其是XIAP和survivin与肿瘤进展之间存在显著相关性。似乎急性髓系白血病（AML）中XIAP的过表达以及急性淋巴细胞白血病（ALL）和DLBCL中survivin的过表达可能成为新的不良预后因素。现在许多研究都集中在评估IAP家族其他蛋白的表达及其意义。本文介绍了目前关于IAPs在血液系统恶性肿瘤中的重要性的知识。
