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

The Wnt/beta-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 II alpha (Topo II alpha) 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 beta-catenin and topo II alpha in a cohort of 59 patients with newly diagnosed AML by immunohistochemistry. Aberrant beta-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 beta-catenin expression nor enhanced topo II alpha activity did. On multivariate survival analysis, four factors independently predicted a shortened overall survival: aberrant beta-catenin expression, high topo II alpha activity, poor-risk cytogenetics, and presence of at least one comorbidity factor. Our results suggest that both beta-catenin and topo II alpha independently predicted an adverse prognosis and might serve as new markers for risk stratification in AML patients. Am. J. Hematol. 84:87-92, 2009. (C) 2008 Wiley-Liss, Inc.