title: Galectin-3 mediates bone marrow microenvironment-induced drug resistance in acute leukemia cells via Wnt/β-catenin signaling pathway.
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.
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. minkaihu@163.com.|Cancer Institute, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. minkaihu@163.com.
authors.forename: Kaimin
authors.initials: K
authors.lastname: Hu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 402575454@qq.com.|Department of Surgical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 402575454@qq.com.
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. loulixia110@zju.edu.cn.
authors.forename: Lixia
authors.initials: L
authors.lastname: Lou
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 150522015@qq.com.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Liu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 37478898@qq.com.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 414567028@qq.com.
authors.forename: Binsheng
authors.initials: B
authors.lastname: Wang
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 781972077@qq.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 11218298@zju.edu.cn.
authors.forename: Jimin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. 11218303@zju.edu.cn.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yu
authors.affiliation: Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310003, China. hehuang.zju@gmail.com.
authors.forename: He
authors.initials: H
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D037502:Galectin 3 / Q000378:metabolism*; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D034741:RNA, Small Interfering; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D059016:Tumor Microenvironment / Q000502:physiology; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000502:physiology*
chemical_list: D037502:Galectin 3; D034741:RNA, Small Interfering