Monitoring of minimal residual disease in acute myeloid leukemia with t(8;21)(q22;q22)

Int J Hematol. 2013 Jun;97(6):786-92. doi: 10.1007/s12185-013-1344-6. Epub 2013 Apr 24.

Abstract

The fusion gene AML1/ETO is a molecular marker for monitoring minimal residual disease (MRD) in acute myeloid leukemia with the t(8;21)(q22;q22) translocation. To evaluate the dynamic variation and prognostic significance of AML1/ETO, bone marrow samples from 52 patients at different periods were examined qualitatively (32 patients) or quantitatively (20 patients) using nested RT-PCR and RQ-PCR, respectively. In the qualitative group, AML1/ETO in 71.88 and 95.45 % patients became negative at six and 24 months after CR, respectively. Patients in long-term remission were all RT-PCR-negative. Patients negative for AML1/ETO at 6-12 months and 12-18 months after CR had lower relapse rate (P = 0.003 and 0.000), higher relapse-free survival (RFS) (P = 0.000 and 0.000), and overall survival (P = 0.001 and 0.000) than patients with positive AML1/ETO. Quantitative analysis showed that there was no trend where higher relapse rate occurred in patients with higher levels of AML1/ETO transcripts at diagnosis (P > 0.05). Patients whose AML1/ETO transcripts decreased by more than 2 log at CR had higher RFS (P = 0.02). At the checkpoints of 3 and 5/6 months after CR, patients with lower AML1/ETO copy numbers showed lower probability of relapse (P = 0.039 and 0.004). An increase of AML1/ETO transcripts (0.5 log) at any time after CR indicated increased risk of relapse (P = 0.002). Our study shows that both qualitative and quantitative detection of AML1/ETO have prognostic value in MRD monitoring. Negative or continuous low expression of AML1/ETO indicates increased disease-free survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Chromosomes, Human, Pair 21*
  • Chromosomes, Human, Pair 8*
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Female
  • Gene Expression
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Middle Aged
  • Neoplasm, Residual / diagnosis*
  • Neoplasm, Residual / genetics*
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • RUNX1 Translocation Partner 1 Protein
  • Translocation, Genetic*
  • Young Adult

Substances

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