WT1 mRNA Level in Peripheral Blood Is a Sensitive Biomarker for Monitoring Minimal Residual Disease in Acute Myeloid Leukemia

Abstract

The Wilms' tumor gene 1 (WT1) encodes a transcription factor that is involved in normal cellular development and cell survival. WT1 mRNA is overexpressed in the minimal residual disease (MRD) of patients with hematopoietic malignancy patients, particularly acute myeloid leukemia (AML). MRD represents the condition with the low levels of leukemia cells in the bone marrow and is known as a sign of recurrence. In hematopoietic malignancies, definition of remission is based on the lack of MRD at submicroscopic level. Between December 2005 and June 2008, we started to measure WT1 mRNA levels in the peripheral blood (PB) from patients by quantitative real-time PCR in Aomori Prefectural Central Hospital. Three hundreds and eight samples from 95 patients were evaluated. The patients included AML (55 patients), acute lymphoblastic leukemia (11), myelodysplastic syndrome (20), malignant lymphoma (5), chronic myeloid leukemia (1), prostatic carcinoma (1), and leukopenia (2). Among the 55 AML patients, 21 patients were pretreated with remission induction therapy. In the clinical course of 21 patients, timely therapeutic approaches could be started for relapse by the early detection of WT1 mRNA overexpression before the morphological findings were apparent. Monitoring WT1 mRNA is helpful to identify patients at high-risk relapse. High overall survival rate (71.2%, 15/21, median: 24.6 months, range 1.1-35.6 months) was achieved in 3 years. The overall survival rate of 34 post-treatment patients was 61.7% (median: 23.5 months, range 0.13-126.5 months after treatment start). In conclusion, the WT1 mRNA level is a sensitive biomarker for monitoring MRD.