Assessment of the contribution of Wnt pathway modulators to acute myeloid leukemia chemosensitivity

Acute myeloid leukemia (AML) is the most common and only partially curable malignant disorder in adults, as drug resistance leading to relapse or refractoriness still remains the major problem in the treatment of patients. Recent studies have demonstrated a dysregulation of Wnt/β-catenin signaling and involvement in the growth and recurrence of various tumors, but its role in AML remains controversial and unclear. In this study, we investigated the role of Wnt/β-catenin signaling in the proliferation, survival and chemoresistance of AML cells either cultured alone or in co-culture with human bone marrow mesenchymal stromal cells (hBM-MSCs). The expression of Wnt pathway components were analyzed in AML cell lines, primary blast cells and hBM-MSCs from healthy donors and AML patients. Moreover, we evaluated whether pharmacologic inhibition of Wnt signaling could affect AML cell viability and sensitivity to chemotherapeutic agents, including Ara-C and Idarubucin. We found that Wnt inhibitors reduced cell proliferation and viability of AML cells both cultured alone and in co-culture with hBM-MSCs , pharmacological inhibition of Wnt signaling significantly enhanced the effects of chemotherapeutic agents AML cell lines and primary blast cells in absence or presence of hBM-MSCs. Our data suggest that targeting Wnt pathway may be a new therapeutic strategy to enhance the effectiveness of chemotherapeutic agents for the treatment of AML.