Expression of ARC (apoptosis repressor with caspase recruitment domain), an antiapoptotic protein, is strongly prognostic in AML
Expression of ARC (apoptosis repressor with caspase recruitment domain), an antiapoptotic protein, is strongly prognostic in AML
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DOI：
10.1182/blood-2010-04-280503
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发表时间：
2011-01-20
期刊：
影响因子：
20.3
通讯作者：
Kornblau, Steven M.
中科院分区：
文献类型：
--
作者：
Carter, Bing Z.;Qiu, Yi Hua;Kornblau, Steven M.
急性髓系白血病(AML)的细胞凋亡调控因子已被广泛研究，并被认为是很好的治疗靶点。带有半胱氨酸天冬氨酸酶招募结构域的凋亡抑制因子(ARC)是一种最初被发现参与心肌细胞凋亡的抗凋亡蛋白，最近被证明在几种实体瘤中过表达。为了评估其在急性髓细胞白血病中的重要性，我们使用一种可靠的反相蛋白质阵列分析了511名新诊断的急性髓细胞白血病患者中ARC的表达，并将ARC水平与临床结果相关联。ARC在AML患者的样本中有不同程度的表达。ARC水平与细胞遗传学类型或Flt-3突变状态无关。然而，ARC蛋白水平低或中等的患者的预后明显好于ARC水平高的患者：总生存期(中位数，53.9或61.6vs38.9周，P=.0015)和缓解时间(中位数，97.6或44.7vs31.1周，P=.0007)。多变量分析表明，ARC是AML患者生存的显著独立预测因素(P=.00013)。抑制ARC可促进OCI-AML3细胞的凋亡，并可致敏阿糖胞苷诱导OCI-AML3细胞的凋亡。这些结果表明，ARC的表达水平对AML的预后有很高的预测作用，ARC是AML潜在的治疗靶点。(《血色》2011；117(3)：780-787)
Regulators of apoptosis in acute myeloid leukemia (AML) have been extensively studied and are considered excellent therapeutic targets. Apoptosis repressor with caspase recruitment domain (ARC), an antiapoptotic protein originally found to be involved in apoptosis of cardiac cells, was recently demonstrated to be overexpressed in several solid tumors. To assess its importance in AML, we profiled ARC expression in 511 newly diagnosed AML patients using a validated robust reverse-phase protein array and correlated ARC levels with clinical outcomes. ARC was variably expressed in samples from patients with AML. ARC level was not associated with cytogenetic groups or with FLT-3 mutation status. However, patients with low or medium ARC protein levels had significantly better outcomes than those with high ARC levels: longer overall survival (median, 53.9 or 61.6 vs 38.9 weeks, P = .0015) and longer remission duration (median, 97.6 or 44.7 vs 31.1 weeks, P = .0007). Multivariate analysis indicated that ARC was a statistically significant independent predictor of survival in AML (P = .00013). Inhibition of ARC promoted apoptosis and sensitized cytosine arabinoside-induced apoptosis in OCI-AML3 cells. These results suggest that ARC expression levels are highly prognostic in AML and that ARC is a potential therapeutic target in AML. (Blood.2011;117(3):780-787)