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Open Access 01-12-2015 | Research

Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway

Authors: Kaimin Hu, Yanjun Gu, Lixia Lou, Lizhen Liu, Yongxian Hu, Binsheng Wang, Yi Luo, Jimin Shi, Xiaohong Yu, He Huang

Published in: Journal of Hematology & Oncology | Issue 1/2015

Abstract

Background

Acute leukemia is currently the major cause of death in hematological malignancies. Despite the rapid development of new therapies, minimal residual disease (MRD) continues to occur and leads to poor outcomes. The leukemia niche in the bone marrow microenvironment (BMM) is thought to be responsible for such MRD development, which can lead to leukemia drug resistance and disease relapse. Consequently further investigation into the way in which the leukemia niche interacts with acute leukemia cells (ALCs) and development of strategies to block the underlying process are expected to improve disease prognosis. Recent studies indicated that galectin-3 (gal-3) might play a pivotal role in this process. Thus we aimed to elucidate the exact role played by gal-3 in this process and clarify its mechanism of action.

Methods

We used human bone marrow-derived mesenchymal stromal cells (hBM-MSCs) to mimic the leukemia BMM in vitro, and investigated their effects on drug resistance of ALCs and the possible mechanisms involved, with particular emphasis on the role of gal-3.

Results

In our study, we demonstrated that hBM-MSCs induced gal-3 up-regulation, promoting β-catenin stabilization and thus activating the Wnt/β-catenin signaling pathway in ALCs, which is critical in cytotoxic drug resistance of leukemia. This effect could be reversed by addition of gal-3 short hairpin RNA (shRNA). We also found that up-regulation of gal-3 promoted Akt and glycogen synthase kinase (GSK)-3β phosphorylation, thought to constitute a cross-bridge between gal-3 and Wnt signaling.

Conclusions

Our results suggest that gal-3, a key factor mediating BMM-induced drug resistance, could be a novel therapeutic target in acute leukemia.

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Title: Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway
Authors: Kaimin Hu
Yanjun Gu
Lixia Lou
Lizhen Liu
Yongxian Hu
Binsheng Wang
Yi Luo
Jimin Shi
Xiaohong Yu
He Huang
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Journal of Hematology & Oncology / Issue 1/2015
Electronic ISSN: 1756-8722
DOI: https://doi.org/10.1186/s13045-014-0099-8

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