Silva K L, Vasconcellos D V, Castro E D de Paula, Coelho A M, Linden R, Maia R C
Laboratório de Hematologia Celular e Molecular, Serviço de Hematologia, Hospital do Câncer I, Instituto Nacional de Câncer, Rio de Janeiro, Brasil.
Apoptosis. 2006 Feb;11(2):277-85. doi: 10.1007/s10495-006-3560-5.
Despite the efficiency of fludarabine in the induction of clinical responses in B-cell chronic lymphocytic leukemia (B-CLL) patients, resistance to this drug has been documented. The present study tested whether resistance to fludarabine is related to the expression of inhibitor of apoptosis proteins (IAPs) family members. We analyzed the expression of c-IAP1, c-IAP2 and XIAP, by immunocytochemistry, in 30 blood samples from B-CLL patients and correlated protein expression to fludarabine-induced apoptosis estimated by an annexin-V assay. Expression of c-IAP1, c-IAP2 and XIAP were found predominantly in the cytoplasm, and a wide range of staining intensities was observed among distinct samples. No correlation was found between the levels of IAPs expression and prognostic factors such as age, gender, lymphocyte doubling time, white blood cell count or previous treatment. The expression of IAPs also failed to predict the sensitivity to fludarabine-induced apoptosis. Alternative pathways of cell death may explain the independence of fludarabine-induced apoptosis from the high expression of IAPs.
尽管氟达拉滨在诱导B细胞慢性淋巴细胞白血病（B-CLL）患者产生临床反应方面具有疗效，但对该药物的耐药性已有文献记载。本研究检测了对氟达拉滨的耐药性是否与凋亡抑制蛋白（IAPs）家族成员的表达有关。我们通过免疫细胞化学分析了30例B-CLL患者血液样本中c-IAP1、c-IAP2和XIAP的表达，并将蛋白表达与通过膜联蛋白-V检测法估算的氟达拉滨诱导的凋亡进行关联。c-IAP1、c-IAP2和XIAP的表达主要位于细胞质中，不同样本间观察到广泛的染色强度范围。未发现IAPs表达水平与年龄、性别、淋巴细胞倍增时间、白细胞计数或既往治疗等预后因素之间存在相关性。IAPs的表达也未能预测对氟达拉滨诱导凋亡的敏感性。细胞死亡的替代途径可能解释了氟达拉滨诱导的凋亡与IAPs高表达无关的现象。
