Wilm’s Tumor 1 Gene Expression Is a Useful Marker for Minimal Residual Disease in Acute Myeloid Leukemia.

One of the difficulties in managing patients with acute myeloid leukemia (AML) is the detection of minimal residual disease. Only a fraction of AML patients have a distinct phenotype on flow cytometry or a genetic abnormality which can be followed as a sensitive marker for minimal residual disease (MRD). The Wilm’s tumor - 1 gene (WT1) is overexpressed in leukemic blasts, but not in normal blood or marrow cells, and thus can be used as a marker for MRD in leukemia patients who otherwise do not have a characteristic immunophenotypic or molecular marker that can be monitored. We prospectively measured serial peripheral blood WT1 levels by RQ-PCR in 54 patients with AML. Of the 54 patients, 23 patients were newly diagnosed. The remaining 31 patients were in complete remission prior to a planned allogeneic transplant. Subsequent WT1 levels were obtained during routine evaluation both during and up to three years after completion of either chemotherapy and/or transplant. Using regression analysis, we found that a normalized WT1 level greater than 10⁻⁴ (as compared to a level of 1 in K562 cells) indicates a higher likelihood of the patient having active leukemia with a sensitivity of 87.5% and a specificity of 89.1%. The positive and negative predictive values are 71.19% and 95.89% respectively. We also compared WT1 levels with peripheral blood and bone marrow blasts to determine whether a correlation existed. We found a strong correlation between WT1 expression and bone marrow blasts with a correlation coefficient of 0.77 (p< 0.0001). A weak correlation was found with peripheral blood blast count (correlation coefficient = 0.35, p<0.0001). Our data implies WT1 can be a useful marker for minimal residual disease in patients with acute myeloid leukemia, especially in patients who do not have an unusual phenotype or molecular marker to monitor MRD.