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

Abstract

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

Induction of β-catenin by the suppression of signal regulatory protein α1 in K562 cells

“…In a survival analysis, they demonstrated that β-catenin appeared as a new independent prognostic factor predicting poor event-free survival and shortened overall survival (23). A similar report was recently published by another group, in which analysis of a cohort of 59 AML patients, demonstrated that high expression of β-catenin is related to shortened overall survival (24).…”

Human CD1D Gene Expression Is Regulated by LEF-1 through Distal Promoter Regulatory Elements

“…Either change can result in the activation of their downstream genes, including oncogene c-MYC and cyclin D1 to promote neoplastic growth (34)(35)(36)(37). Aberrant expression of b-catenin, which plays a central role in Wnt signaling, is associated with a poor prognosis in patients with acute myeloid leukemia (38,39). Interestingly, a recent study showed that a subgroup of patients with acute lymphoblastic leukemia was associated with a poor prognosis when the leukemia cells express CD1d (40).…”

Selective treatment of mixed-lineage leukemia leukemic stem cells through targeting glycogen synthase kinase 3 and the canonical Wnt/β-catenin pathway

“…Conversely, genetic or pharmacological suppression of b-catenin expression inhibited leukemogenic transformation mediated by MLL fusions or Hoxa9/MEIS1, revealing its essential function in leukemic transformation [31 & ,32 && ]. In human AML, elevated b-catenin expression is also associated with high relapse rate and poor overall survival [33,34]. Elevated expression of b-catenin enhanced blastreplating efficiency [33].…”