Tian Yiming, Huang Zoufang, Wang Zhixiang, Yin Changxin, Zhou Lanlan, Zhang Lingxiu, Huang Kaikai, Zhou Hongsheng, Jiang Xuejie, Li Jinming, Liao Libin, Yang Mo, Meng Fanyi
Hematology Department of Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, China.
Bioinformatics Department, Southern Medical University, Guangzhou, Guangdong Province, China.
PLoS One. 2014 Jan 8;9(1):e84150. doi: 10.1371/journal.pone.0084150. eCollection 2014.
Numerous factors impact on the prognosis of acute myeloid leukemia (AML), among which molecular genetic abnormalities are developed increasingly, however, accurate prediction for newly diagnosed AML patients remains unsatisfied. For further improving the prognosis evaluation system, we investigated the transcripts levels of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 in 97 AML patients and 30 non-malignant controls, and validated using the published microarray data from 225 cytogenetically normal AML (CN-AML) patients treated according to the German AMLCG-1999 protocol. Real-time quantitative polymerase chain reaction and western blot were carried out, and clinical data were collected and analyzed. High Ang2 and FIS1 expression discriminated the CR rate of AML patients (62.5% versus 82.9% for Ang2, P = 0.011; 61.4% versus 82.2% for FIS1, P = 0.029). In CN-AML, patients with high FIS1 expression were more likely to be resistant to two courses of induction (P = 0.035). Overall survival (OS) and relapse-free survival (RFS) were shorter in CN-AML patients with high PDCD7 expression (P<0.001; P = 0.006), and PDCD7 was revealed to be an independent risk factor for OS in CN-AML (P = 0.004). In the analysis of published data from 225 CN-AML patients, PDCD7 remained independently predicting OS in CN-AML (P = 0.039). As a conclusion, Ang2 and FIS1 seem related to decreased CR rate of AML patients, and PDCD7 is associated with shorter OS and RFS in CN-AML. Hence, PDCD7, Ang2 and FIS1 may indicate a more aggressive form and poor prognosis of AML.
众多因素影响急性髓系白血病（AML）的预后，其中分子遗传学异常日益受到关注，然而，对新诊断的AML患者的准确预测仍不尽人意。为进一步完善预后评估系统，我们检测了97例AML患者和30例非恶性对照中PDCD7、FIS1、FAM3A、CA6、APP、KLRF1、ATCAY、GGT5和Ang2的转录水平，并使用根据德国AMLCG-1999方案治疗的225例细胞遗传学正常AML（CN-AML）患者的已发表微阵列数据进行验证。进行了实时定量聚合酶链反应和蛋白质印迹分析，并收集和分析了临床数据。高Ang2和FIS1表达可区分AML患者的完全缓解率（Ang2为62.5%对82.9%，P = 0.011；FIS1为61.4%对82.2%，P = 0.029）。在CN-AML中，FIS1高表达的患者对两个疗程诱导治疗更可能耐药（P = 0.035）。PDCD7高表达的CN-AML患者总生存期（OS）和无复发生存期（RFS）较短（P<0.001；P = 0.006），并且PDCD7被揭示为CN-AML中OS的独立危险因素（P = 0.004）。在对225例CN-AML患者的已发表数据进行分析时，PDCD7在CN-AML中仍可独立预测OS（P = 0.039）。结论是，Ang2和FIS1似乎与AML患者完全缓解率降低有关，而PDCD7与CN-AML中较短的OS和RFS相关。因此，PDCD7、Ang第2和FIS1可能表明AML具有更侵袭性的形式和不良预后。
