Wilms’ Tumor Gene (WT1) Expression and Minimal Residual Disease in Acute Myeloid Leukemia

ABSTRACT

The identification of minimal residual disease (MRD) has led to substantial improvements in early recognition of the recurrence of acute myeloid leukemia (AML). Flow cytometry (FC), real-time quantitative polymerase chain reaction (RQ-PCR) and fluorescence in situ hybridization are useful methods for the detection of MRD in AML patients although molecular monitoring of leukemia-specific rearranged (RUNX1-RUNX1T1 and CBFB-MYH11) or mutated genetic (NPM1, CEBPA) sequences represents the most sensitive methodology. Besides, more than 50% of all AML patients lack one of these specific sequences, so it is crucial to identify molecular targets applicable for the majority of patients. WT1 is overexpressed at the mRNA level in 80–90% of AML cases at diagnosis in both peripheral blood and bone marrow, and is detectable in a consistent low range in normal donors. These features have led to its adoption for MRD detection using RQ-PCR. A European LeukemiaNet Study found the magnitude of WT1 log reduction after induction chemotherapy to be an independent predictor of relapse. Other studies showed a poorer outcome in patients having WT1 levels above reference thresholds at specific time points. WT1 expression was compared with other modalities of MRD assessment, such as RQ-PCR of specific fusion genes and FC, but no differences in terms of predictive value emerged. Finally, some authors translated the use of WT1 in the clinic giving donor lymphocytes infusions to patients with increasing WT1-mRNA levels after allogeneic stem cell transplantation and obtaining an improvement of survival in this subset. Data collected on WT1 expression over the past years provided evidence for the use of this molecular marker to stratify high-risk AML patients. It can also be used as a marker for early interventional therapy, but further studies are needed to demonstrate it.