Galectin-3 in pre-B acute lymphoblastic leukemia

Fei, F; Abdel‐Azim, Hisham; Lim, Min; Arutyunyan, Anna; Itzstein, Mark von; Groffen, John; Heisterkamp, Nora

doi:10.1038/leu.2013.175

Cited by 32 publications

(38 citation statements)

References 15 publications

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“…Secreted gal-3 was critical for the immunomodulatory potency of hUC-MSCs. It was also mentioned that OP9 cells also secreted gal-3 and that some of the gal-3 detected on pre-B ALL cells was of stromal origin [ 17 ]. The role of gal-3 derived from stromal cells and the potential mechanisms involved in its action in leukemia therefore deserve further study.…”

Section: Discussionmentioning

confidence: 99%

“…It has roles in cell growth, apoptosis, adhesion, tumor angiogenesis, malignant cell metastasis, cancer-matrix interaction and also cancer drug resistance [ 14 , 15 ]. Recent evidence revealed that gal-3 was up-regulated in Ph + chronic myeloid leukemia (CML) and in pre-B ALL after conditioning with BM stromal cells [ 16 , 17 ]. Cheng and colleagues [ 18 ] reported that in patients with AML, higher bone marrow LGALS3 ( gal - 3 ) gene expression was an independent unfavorable prognostic factor for overall survival.…”

Section: Introductionmentioning

confidence: 99%

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

Lou

et al. 2015

J Hematol Oncol

130

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BackgroundAcute 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.MethodsWe 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.ResultsIn 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.ConclusionsOur 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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Lou

et al. 2015

J Hematol Oncol

130

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“…the localization of CML cells to the BMM (Yamamoto-Sugitani et al, 2011). More recently, galectin-3 was found to be elevated in the serum and ex vivo studies showed that galectin-3 also originates from stromal cells besides leukemic cells in B-ALL (Fei et al, 2013). In another study, soluble or stroma-cell-bound galectin-3 was taken up by ALL cells, where it modulates the NF-κB pathway and protects pre-B ALL cells from chemotherapeutic agents (Fei et al, 2015).…”

Section: Role Of the Bmm In Chemoresistancementioning

confidence: 98%

The bone marrow microenvironment in health and disease at a glance

Kumar

Godavarthy

Krause

2018

Journal of Cell Science

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The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem cells, as well as of malignant processes that can develop there. Multiple and complex interactions with the BMM influence hematopoietic stem cell (HSC) physiology, but also the pathophysiology of hematological malignancies. Reciprocally, hematological malignancies alter the BMM, in order to render it more hospitable for malignant progression. In this Cell Science at a Glance article and accompanying poster, we highlight concepts of the normal and malignant hematopoietic stem cell niches. We present the intricacies of the BMM in malignancy and provide approaches for targeting the interactions between malignant cells and their BMM. This is done in an effort to augment existing treatment strategies in the future.

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“…Forced overexpression of galectin-3 in these cells was sufficient to confer chemoresistance in the absence of BMSCs [48] . Consistent with these findings, Fei et al [49] found that in vitro, patient-derived B-ALL cells harvested from underneath a BMSC feeder cell layer, where they maintained direct cell-cell contact with feeder cells, had more galectin-3 on their cell surface relative to cells found in suspension above the cell layer or cells cultured in the absence of BMSCs. These same authors went on to assess secreted galectin-3 levels in the growth medium from BMSCs cultured in the absence or presence of ALL cells, and found that BMSCs secreted more galectin-3 in the context of ALL cell co-culture relative to culture of BMSCs alone, while ALL cells alone did not secrete galectin-3 under any conditions.…”

Section: Galectinsmentioning

confidence: 72%

The bone marrow microenvironment as a mediator of chemoresistance in acute lymphoblastic leukemia

Meyer¹,

Hermiston²

2019

CDR

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Acute lymphoblastic leukemia (ALL) is a malignancy of immature lymphoid cells that arises due to clonal expansion of cells that undergo developmental arrest and acquisition of pathogenic mutations. With the introduction of intensive multi-agent chemotherapeutic regimens, survival rates for ALL have improved dramatically over the past several decades, though survival rates for adult ALL continue to lag behind those of pediatric ALL. Resistance to chemotherapy remains a significant obstacle in the treatment of ALL, and chemoresistance due to molecular alterations within ALL cells have been described. In addition to these cell-intrinsic factors, the bone marrow microenvironment has more recently been appreciated as a cell-extrinsic mediator of chemoresistance, and it is now known that stromal cells within the bone marrow microenvironment, through direct cell-cell interactions and through the release of lymphoid-acting soluble factors, contribute to ALL pathogenesis and chemoresistance. This review discusses mechanisms of chemoresistance mediated by factors within the bone marrow microenvironment and highlights novel therapeutic strategies that have been investigated to overcome chemoresistance in this context.

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Galectin-3 in pre-B acute lymphoblastic leukemia

Cited by 32 publications

References 15 publications

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

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

The bone marrow microenvironment in health and disease at a glance

The bone marrow microenvironment as a mediator of chemoresistance in acute lymphoblastic leukemia

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