Targeting human Acute Myelogenous Leukemia stem cells by inhibiting aberrant Wnt/beta-catenin signaling

Acute Myelogenous Leukemia (AML) is a hematological malignancy. The majority of patients die from persistent or relapsed AML. Leukemic Stem Cells (LSCs) are believed to cause relapse, and current chemotherapies do not target LSCs effectively. Previous studies have found that activation of Wnt/beta-catenin signaling is required for LSC self-renewal. We hypothesized that targeting of Wnt/beta-catenin signaling could selectively eliminate LSCs. To study the in vitro effect of Wnt/beta-catenin signaling inhibition on LSCs, we exposed CD34+ stem/progenitor cells from AML patients (n=8) to two Wnt signaling inhibitors. Treated cells were tested for viability and functionality using CFSE proliferation assay, Annexin V apoptosis assay, LumiGlo ATP quantification assay, colony formation assay, and RT-qPCR. Our data demonstrate that Wnt signaling protein secretion and beta-catenin/CBP interaction are important components of Wnt/beta-catenin signaling in proliferation of LSCs. However, neither of the drugs was effective in inducing apoptosis or in altering Wnt target gene expression consistently