Prognostic value of AML 1/ETO fusion transcripts in patients with acute myelogenous leukemia

Korean J Intern Med. 2003 Mar;18(1):13-20. doi: 10.3904/kjim.2003.18.1.13.

Abstract

Background: The t (8;21) (q22;q22), which produces the fusion gene AML1/ETO, is associated with relatively good prognosis and, in particular, with a good response to cytosine arabinoside. Analysis of t (8;21) positive leukemic blasts has shown characteristic morphological and immunological features. We performed this study to investigate the incidence of AML1/ETO rearrangement in adult acute myelogenous leukemia (AML), especially in M2 subtype, to make a comparison of clinical, morphological and immunophenotypic characteristics between AML1/ETO rearrangement positive and negative group in patients with AML and to analyze the correlation with other biological parameters.

Methods: From May 1995 to Sept. 2000, fifty-nine patients with AML, including twenty-nine AML-M2, were studied. RNAs were extracted from leukemic cells and reverse transcriptase mediated polymerase chain reaction (RT-PCR) for AML1/ETO fusion transcript was done. Chromosome study, immunophenotypic and clinical characteristics were analyzed and statistical analysis was done.

Results: The incidence of AML1/ETO fusion transcripts was 22.0% in AML and 44.8% in AML-M2. The morphologic finding of bone marrow in AML-M2 showed higher incidence of Auer rods, large blast with prominent golgi and abnormal granules in AML1/ETO positive patients. There was no significant difference of immunophenotype. AML patients with AML1/ETO had a tendency of higher complete remission rate (81.8% vs 56.6%, p = 0.13). The overall survival (median; 82.2 weeks vs 34.4 weeks, p = 0.02) and progression free survival (median; 50.9 weeks vs 20.4 weeks, p = 0.02) of AML1/ETO positive group were longer than those of the negative group in AML. AML-M2 patients with AML1/ETO rearrangement had also a tendency of longer overall survival and progression free survival, although there was no significant difference between both groups.

Conclusion: Our data suggest that AML1/ETO rearrangement is detected frequently in AML, especially M2, and is a favorable prognostic factor. Thus, molecular diagnostic approaches should be used routinely to identify patients with this gentic subtype of AML.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Base Sequence
  • Cohort Studies
  • Confidence Intervals
  • Core Binding Factor Alpha 2 Subunit
  • Female
  • Gene Expression Regulation, Leukemic*
  • Genetic Predisposition to Disease*
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / genetics*
  • Prognosis
  • Prospective Studies
  • RUNX1 Translocation Partner 1 Protein
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Survival Analysis
  • Transcription Factors / genetics*
  • Translocation, Genetic
  • Treatment Outcome

Substances

  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Oncogene Proteins, Fusion
  • RUNX1 Translocation Partner 1 Protein
  • Transcription Factors