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Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

ABSTRACT: 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.

SUBMITTER: Tian Y

PROVIDER: S-EPMC3885535 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

Tian Yiming Y Huang Zoufang Z Wang Zhixiang Z Yin Changxin C Zhou Lanlan L Zhang Lingxiu L Huang Kaikai K Zhou Hongsheng H Jiang Xuejie X Li Jinming J Liao Libin L Yang Mo M Meng Fanyi F

PloS one 20140108 1

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 cytogen ...[more]

PMID: 24416201

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Project description:Secreted frizzled-related proteins (SFRPs) as Wnt signaling antagonists have been found to be dysregulated by promoter hypermethylation in several cancers including acute myeloid leukemia (AML). This study aimed to investigate the methylated status of SFRPs promoter region and its clinical relevance in Chinese non-M3 AML patients.SFRPs methylation in 139 primary non-M3 AML patients was determined using methylation-specific real-time quantitative polymerase chain reaction.The frequency of aberrant methylation was as follows: 30.2% for SFRP1, 27.3% for SFRP2, 5.0% for SFRP4, and 1.4% for SFRP5. Hypermethylation of at least one SFRP gene occurred in 51.8% (72/139) of non-M3 AML patient samples, which was significantly higher compared to normal control (0/21) (P<0.001). Hypermethylation of SFRP1 was potentially associated with N/K-RAS mutations (P=0.043), and the frequency of SFRPs methylation was higher in patients ≥50 years compared to those <50 years, especially for SFRP2 (P<0.05). Furthermore, both whole cohort and cytogenetically normal (CN) patients with high SFRPs-methylated group showed a shorter overall survival (OS) compared to those with low group (P=0.036 and P=0.035, respectively). Moreover, Cox regression multivariate analysis revealed that SFRPs hypermethylation acts as an independent prognostic biomarker among both whole cohort (hazard ratio =1.804, P=0.026) and CN (hazard ratio =2.477, P=0.023) patients. In leukemic cell line HL60 treated with 5-aza-2'-deoxycytidine, the alteration of SFRP1/2 expression inversely correlated with change in SFRP1/2 methylation (r=-0.975, P=0.005 and r=-0.975, P=0.005, respectively). A tendency of negative correlation was observed between SFRP1 expression and its promoter methylation in AML patients (r=-0.334, P=0.038).These findings suggested that hypermethylation of SFRP1/2 was a frequent event and silenced SFRP1/2 expression in AML. Moreover, hypermethylation of SFRPs promoter was an adverse risk factor for OS in Chinese non-M3 AML patients.

Dataset Information

Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

Publications

Identification of novel molecular markers for prognosis estimation of acute myeloid leukemia: over-expression of PDCD7, FIS1 and Ang2 may indicate poor prognosis in pretreatment patients with acute myeloid leukemia.

Similar Datasets

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