ISSN 2997-1036
International Journal of Hematology | Vol. 12, No. 3, March 2021 | pp. 17–24
DOI: 10.46882/2021/IJH/000133
Review Article
Title: Targeting the Wnt/beta-catenin Signaling Pathway in Acute Myeloid Leukemia Stem Cells: Mechanisms and Inhibition
Names of Authors: M. A. Bello¹, O. R. Eze²
Authors’ Affiliations: ¹Department of Haematology, Aminu Kano Teaching Hospital, Kano, Nigeria; ²Department of Pathology, University of Benin, Benin City, Nigeria
Abstract: Quiescent leukemia stem cells escape standard cytotoxic chemotherapy, driving disease relapse and resistance in acute myeloid leukemia. This comprehensive review examines the cellular mechanisms of the evolutionary conserved Wnt/beta-catenin signaling pathway in sustaining leukemia stem cell self-renewal and marrow niche interactions. Accumulation of beta-catenin in the nucleus complexes with TCF/LEF transcription factors, upregulating critical cell-survival and proliferative genes. Traditional intensive chemotherapy regimens fail to eliminate these slow-cycling progenitors. Evolving management models emphasize the therapeutic deployment of small-molecule Wnt/beta-catenin inhibitors. Combining targeted catenin path inhibitors with low-dose cytarabine or hypomethylating backbones has shown clinical efficacy in expanding overall survival in elderly or frail acute myeloid leukemia populations unsuited for standard induction. However, secondary drug resistance can emerge via alternative microenvironmental niche overrides or signaling crosstalk. This review outlines clear biomarker tracking networks, beta-catenin expression monitoring, and combination protocols designed to bypass intrinsic resistance pathways and optimize clonal eradication in myeloid leukemias.
Keywords: Acute myeloid leukemia, leukemia stem cells, Wnt/beta-catenin pathway, molecular inhibitors, clonal resistance
Manuscript Timeline: Received: December 01, 2020; Revised: January 12, 2021; Accepted: February 04, 2021; Published: March 15, 2021