ISSN 2997-1036
International Journal of Hematology | Vol. 11, No. 3, March 2020 | pp. 17–24
DOI: 10.46882/2020/IJH/000123
Review Article
Title: Cellular mechanisms and targeted molecular inhibition of the hedgehog signaling pathway in acute myeloid leukemia stem cells
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 Hedgehog signaling pathway in sustaining leukemia stem cell self-renewal and marrow niche interactions. Binding of Hedgehog ligands to Patched receptors relieves inhibition on Smoothened (SMO), triggering downstream activation of GLI transcription factors and upregulating cell-survival pathways. Traditional intensive chemotherapy regimens fail to eliminate these slow-cycling progenitors. Evolving management models emphasize the therapeutic deployment of small-molecule Smoothened inhibitors, such as glasdegib. Combining glasdegib 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 novel Smoothened mutations or crosstalk with the bone marrow microenvironment. This review outlines clear biomarker tracking networks, GLI 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, hedgehog pathway, glasdegib, smoothened inhibitor
Manuscript Timeline: Received: December 01, 2019; Revised: January 12, 2020; Accepted: February 04, 2020; Published: March 15, 2020