Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML
Intact apoptosis signaling in myeloid leukemia cells determines treatment outcome in childhood AML
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DOI：
10.1182/blood-2007-08-109058
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发表时间：
2008-03-01
期刊：
影响因子：
20.3
通讯作者：
Debatin, Klaus-Michael
中科院分区：
文献类型：
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作者：
Meyer, Lueder H.;Queudeville, Manion;Debatin, Klaus-Michael
最近，我们报道了完整的细胞凋亡信号预示着儿童急性淋巴细胞白血病的良好预后。在这里，我们在45名儿童急性髓系白血病患者中解决了这个问题，分析了两个核心的细胞凋亡事件：细胞色素c的释放和caspase-3的激活。在预后良好的患者中，细胞色素c的释放明显依赖于caspase，并与激活的caspase-3相关，这表明caspase-8等启动子或放大因子的激活以及完整的凋亡体功能是良好预后的基础。Caspase依赖的细胞色素c相关的caspase-3激活(CRAC(Dep))参数反映了这一促凋亡检查点的功能完整性。CRACdep阳性的患者(信号完整)与CRAC(DEP)阴性的患者(信号缺陷)相比，存活率更高。因此，白血病细胞发生凋亡的倾向是良好治疗结果的重要特征，可作为儿童AML患者的额外分层工具。这项试验已在WWW上注册。ClinicalTrials.gov AS#NCT00111345。
Recently we reported that intact apoptosis signaling is indicative of favorable outcome in childhood acute lymphoblastic leukemia. Here we addressed this issue in 45 pediatric acute myeloid leukemia patients analyzing 2 core apoptogenic events: cytochrome c release and caspase-3 activation. In patients with good prognosis cytochrome c release was clearly found to be caspase-dependent and correlated with activated caspase-3, indicating that activation of initiator or amplifier caspases such as caspase-8 together with an intact apoptosome function are elementary for favorable outcome. The functional integrity of this apoptogenic checkpoint is reflected by the parameter caspase-dependent cytochrome c-related activation of caspase-3 (CRAC(dep)). Patients with positive CRACdep values (intact signaling) exhibited superior survival compared with CRAC(deP) negative patients (deficient signaling). Thus, the propensity to undergo apoptosis of leukemia cells is an important feature for favorable treatment outcome and may serve as an additional stratification tool for pediatric AML patients. This trial was registered at www. ClinicalTrials.gov as #NCT00111345.