Mcl-1 依赖性预测急性髓细胞白血病对伏立诺他和吉妥珠单抗奥佐米星的反应。
Mcl-1 dependence predicts response to vorinostat and gemtuzumab ozogamicin in acute myeloid leukemia.
机构信息
Eutropics Pharmaceuticals, Inc., Cambridge, MA, United States.
Eutropics Pharmaceuticals, Inc., Cambridge, MA, United States.
出版信息
Leuk Res. 2014 May;38(5):564-8. doi: 10.1016/j.leukres.2014.02.007. Epub 2014 Feb 28.
Abstract
Older adults with acute myeloid leukemia (AML) are commonly considered for investigational therapies, which often only benefit subsets of patients. In this study, we assessed whether BH3 profiling of apoptotic functionality could predict outcomes following treatment with vorinostat (histone deacetylase inhibitor) and gemtuzumab ozogamicin (GO; CD33-targeted immunoconjugate). Flow cytometry of BH3 peptide priming with Noxa (anti-apoptotic protein Mcl-1 modulator) correlated with remission induction (p=.026; AUC=0.83 [CI: 0.65-1.00; p=.00042]: AUC=0.88 [CI:0.75-1.00] with age adjustment) and overall survival (p=.027 logistic regression; AUC=0.87 [0.64-1.00; p=.0017]). This Mcl-1-dependence suggests a pivotal role of Bcl-2 family protein-mediated apoptosis to vorinostat/GO in AML patients.
摘要
老年急性髓系白血病 (AML) 患者通常被认为适合接受试验性治疗，但这些治疗方法通常仅对部分患者有效。在这项研究中，我们评估了凋亡功能的 BH3 谱分析是否可以预测伏立诺他（组蛋白去乙酰化酶抑制剂）和吉妥珠单抗奥唑米星（CD33 靶向免疫偶联物）治疗后的结局。Noxa（抗凋亡蛋白 Mcl-1 调节剂）BH3 肽引发的流式细胞术与缓解诱导相关（p=.026；AUC=0.83 [CI：0.65-1.00；p=.00042]：年龄调整后 AUC=0.88 [CI：0.75-1.00]）和总生存（p=.027 逻辑回归；AUC=0.87 [0.64-1.00；p=.0017]）。这种对 Mcl-1 的依赖性表明，Bcl-2 家族蛋白介导的凋亡在 AML 患者中对伏立诺他/GO 具有关键作用。
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