Wilms’ tumor gene 1 expression can predict sudden disease progression to blast crisis in patients with chronic myeloid leukemia receiving imatinib therapy

Abstract

Background The Philadelphia chromosome is the hallmark of chronic myeloid leukemia (CML). As the disease progresses to accelerated phase and blast crisis (BC), clonal evolution may occur with the emergence of additional chromosomal abnormalities. Wilms’ tumor 1 gene (WT1) plays an important role in leukemogenesis, and its expression could represent a useful molecular marker of hematological malignancies. Aim The aim of this study was to evaluate WT1 expression and compare its kinetics with that of BCR-ABL1 expression in peripheral blood of patients with CML, to explore the utility of WT1 as an alternative marker for prediction of early disease progression and sudden transformation to BC. Patients and Methods A total of 49 newly diagnosed patients with CML, and 20 normal individuals as controls were enrolled in this study. WT1 and BCR-ABL1 expression was evaluated by quantitative real-time PCR. Results There was significant correlation between the expression of WT1 and BCR-ABL1 only at diagnosis and after 3 and 6 months of therapy. At 12 months of follow-up, an increase in %WT1 associated with low BCR-ABL1 was noticed in two of cases. One case suddenly progressed to BC at 18 months, and the other case showed emergence of clonal chromosome abnormality (+8) and progressed to accelerated phase. Conclusion Our results suggested that serial assessment of WT1 transcript level in patients with CML may be a useful marker for predicting early and sudden disease progression into advanced stages.