Monitoring the AML1/ETO fusion transcript to predict outcome in childhood acute myeloid leukemia

Pediatr Blood Cancer. 2014 Oct;61(10):1761-6. doi: 10.1002/pbc.25109. Epub 2014 Jun 11.

Abstract

Background: To determine the prognostic significance of the detection of the minimal residual disease (MRD) in children with AML1/ETO AML, we compared the results of reverse-transcription polymerase chain reaction (RT-PCR) and quantitative reverse-transcription polymerase chain reaction (RQ-PCR).

Procedure: Between January 2006 and February 2013, 70 patients (≤16 years of age) with AML1/ETO AML were included in our study. Bone marrow samples were evaluated using by both RT-PCR and RQ-PCR assays. AML1/ETO transcripts were normalized to 10(5) ABL copies.

Results: When treated with fewer than four courses of therapy, no association was found between positive RT-PCR results and relapse. After four courses of therapy, a positive RT-PCR result was correlated with a probability of relapse. After induction chemotherapy, a >1.8 log reduction in AML1/ETO transcripts in BM determined by RQ-PCR may represent a subgroup of patients at low risk for relapse. MRD levels after consolidation (Courses 2 and 3) were also informative.

Conclusion: Both RT-PCR and RQ-PCR can be used to detect MRD in childhood AML1/ETO AML. RQ-PCR can identify patients who are at high risk of relapse earlier than can RT-PCR.

Keywords: AML1/ETO; acute; child; leukemia; myeloid; polymerase chain reaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Biomarkers, Tumor / genetics
  • Child
  • Child, Preschool
  • Core Binding Factor Alpha 2 Subunit / analysis*
  • Core Binding Factor Alpha 2 Subunit / genetics
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / mortality
  • Male
  • Neoplasm, Residual
  • Oncogene Proteins, Fusion / analysis*
  • Oncogene Proteins, Fusion / genetics
  • Prognosis
  • Proportional Hazards Models
  • ROC Curve
  • RUNX1 Translocation Partner 1 Protein
  • Real-Time Polymerase Chain Reaction*
  • Reverse Transcriptase Polymerase Chain Reaction*
  • Transcription, Genetic
  • Treatment Outcome

Substances

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