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Galectin-1 and Galectin-3 in B-Cell Precursor Acute Lymphoblastic Leukemia
Fei Fei1, Mingfeng Zhang2, Somayeh S Tarighat1
1Section of Molecular Carcinogenesis, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, The Saban Research Institute of Children's Hospital, Los Angeles, CA 90027, USA.
International Journal of Molecular Sciences
|November 26, 2022
Summary
Blocking Galectin-1 and Galectin-3 in bone marrow stromal cells can reduce chemotherapy resistance in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Targeting these galectins enhances drug sensitivity and may improve BCP-ALL treatment outcomes.
Area of Science:
- Immunology and Cancer Biology
- Glycobiology and Molecular Therapeutics
Background:
- B-cell precursor acute lymphoblastic leukemia (BCP-ALL) exhibits chemotherapy resistance due to intrinsic factors and bone marrow stromal cell interactions.
- Galectins, specifically Galectin-1 and Galectin-3, are lectins expressed by stromal and hematopoietic cells, influencing BCP-ALL survival.
- Galectin-3 expression is modulated by chemotherapy, suggesting a dynamic role in drug resistance.
Purpose of the Study:
- To investigate the roles of Galectin-1 and Galectin-3 in BCP-ALL chemoresistance within the bone marrow microenvironment.
- To evaluate the therapeutic potential of inhibiting Galectin-1 and Galectin-3 interactions using plant-derived carbohydrates.
Main Methods:
- Comparison of Galectin-1 x Galectin-3 double null mutant murine BCP-ALL cells with wild-type cells.
- Inhibition of extracellular Galectin-1/-3 binding using plant-derived carbohydrates (GM-CT-01, GR-MD-02) in co-cultures.
- Assessment of BCP-ALL cell migration, proliferation, and drug sensitivity.
- Analysis of ST6Gal1 knockdown cells co-cultured with Galectin-1 or Galectin-3 knockout stromal cells.
Main Results:
- Double knockout of Galectin-1 and Galectin-3 in BCP-ALL cells reduced migration, inhibited proliferation, and increased drug sensitivity.
- Carbohydrate inhibitors GM-CT-01 and GR-MD-02 attenuated BCP-ALL cell migration and sensitized human BCP-ALL cells to vincristine and nilotinib.
- Stromal Galectin-3 was crucial for BCP-ALL survival during chemotherapy; stromal Galectin-1 had a lesser role.
- ST6Gal1-mediated N-glycan sialylation did not significantly impact drug resistance in this context.
Conclusions:
- Galectin-1 and Galectin-3 have complex, overlapping roles in BCP-ALL survival, with distinct contributions from endogenous and stromal sources.
- Targeting both extracellular and intracellular Galectin-1 and Galectin-3 is essential for overcoming BCP-ALL persistence in the bone marrow niche.
- Inhibition of galectin interactions presents a promising strategy to enhance chemotherapy efficacy against BCP-ALL.
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