Quantification of AML1-ETO fusion transcript as a prognostic indicator in acute myeloid leukemia

Abstract

BACKGROUND AND OBJECTIVES: In spite of the high complete remission rate that chemotherapy achieves in acute myeloid leukemia with AML1-ETO gene rearrangement, relapse is a major cause of treatment failure in this condition. We aimed to determine a predictor of relapse with the real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) of AML1-ETO chimeric mRNA. DESIGN AND METHODS: We serially monitored AML1-ETO fusion transcripts using RQ-PCR in 113 bone marrow or peripheral blood samples from 21 patients with AML1-ETO-positive acute myeloid leukemia and analyzed the prognostic relevance of the results. RESULTS: Higher transcript levels at diagnosis were associated with a higher probability of relapse (p=0.038 in all patients and p=0.001 in adult patients). A decrease of less than 3-log at the time of achieving complete remission was also associated with a higher risk of relapse (p=0.035 in all patients and p=0.011 in adult patients). RQ-PCR detected the reappearance of AML1-ETO fusion transcripts in both peripheral blood and bone marrow during apparent complete remission. Detection of the transcripts preceded hematologic relapse by one to three months. The transcript levels in peripheral blood correlated with those in bone marrow at the same time point. INTERPRETATION AND CONCLUSIONS: Our findings indicate that regular monitoring of AML1-ETO chimeric transcript levels by RQ-PCR on bone marrow or peripheral blood samples could be extremely useful for the selection of high-risk patients and be an early predictor of relapse.