Prognostic significance of β-catenin and topoisomerase IIα in de novo acute myeloid leukemia

The Wnt/β-catenin signaling is important for controlling self-renewal of hematopoietic stem cells and its constitutive activation has recently been documented in a significant proportion of acute myeloid leukemia (AML) cases. Topoisomerase IIα (Topo IIα) is a marker of cell proliferation and a crucial target for anthracycline cytotoxicity, the mainstay of management employed in AML. We retrospectively investigated the prognostic roles of β-catenin and topo IIα in a cohort of 59 patients with newly diagnosed AML by immunohistochemistry. Aberrant β-catenin expression was demonstrated in 13 patients (22%), and it was more likely to occur in those with unfavorable karyotypes. Advanced age and poor performance status adversely influenced the achievement of complete remission, while neither aberrant β-catenin expression nor enhanced topo IIα activity did. On multivariate survival analysis, four factors independently predicted a shortened overall survival: aberrant β-catenin expression, high topo IIα activity, poor-risk cytogenetics, and presence of at least one comorbidity factor. Our results suggest that both β-catenin and topo IIα independently predicted an adverse prognosis and might serve as new markers for risk stratification in AML patients. Am. J. Hematol.