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.

Highlights

  • Acute myeloid leukemia (AML) is a clonal hematopoietic stem cell malignancy with highly heterogeneity

  • Expression data of PDCD7, FIS1, FAM3A, CA6, APP, KLRF1, ATCAY, GGT5 and Ang2 were analyzed in 97 AML patients and 30 non-malignant controls, as well as published data of PDCD7 expression from 225 cytogenetically normal AML (CN-AML) patients treated with a uniform protocol

  • Overall survival (OS) and relapse-free survival (RFS) were not influenced by high versus low Ang2 and FIS1 expression in CN-AML (Ang2, OS: hazard ratio (HR) 1.046; 95% confidence interval (CI), 0.657–1.665; P = 0.851; RFS: HR, 1.471; 95% CI, 0.714–3.029; P = 0.295

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Summary

Introduction

Acute myeloid leukemia (AML) is a clonal hematopoietic stem cell malignancy with highly heterogeneity. The prognostic prediction for AML had been improved tremendously in the past decades, accurate risk-stratification at diagnosis remained difficult. Twenty-two molecular targets, which are potentially associated with complete remission (CR) durations of AML, has been selected based on our previous gene-chip study [2]. The study included 6 AML patients, three of them relapsed in 6–12 months and died within 3 months after relapse, the other three achieved and sustained CR status over 1 year. From the 22 targets, eight genes with clear gene fuctions were selected as prognostic candidates and investigated in our present study, including GGT5, FAM3A, PDCD7, FIS1, CA6, ATCAY, KLRF1 and APP

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