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

PLoS One. 2014 Jan 8;9(1):e84150. doi: 10.1371/journal.pone.0084150. eCollection 2014.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis Regulatory Proteins / genetics*
  • Apoptosis Regulatory Proteins / metabolism
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cytogenetic Analysis
  • Female
  • Gene Expression Regulation, Leukemic
  • Humans
  • Immunoblotting
  • Lectins, C-Type / genetics
  • Lectins, C-Type / metabolism
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / genetics*
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Multivariate Analysis
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • Receptors, Natural Killer Cell / genetics
  • Receptors, Natural Killer Cell / metabolism
  • Recurrence
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Treatment Outcome
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism
  • Young Adult

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers, Tumor
  • FIS1 protein, human
  • KLRF1 protein, human
  • Lectins, C-Type
  • Membrane Proteins
  • Mitochondrial Proteins
  • PDCD7 protein, human
  • Receptors, Natural Killer Cell
  • Transcription Factors
  • VPS51 protein, human
  • Vesicular Transport Proteins

Grants and funding

This work is supported by grants from the National Science Foundation of Guangdong Province, China (S20110100003807), the funders have no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.