B-cell precursor acute lymphoblastic leukemia and stromal cells communicate through Galectin-3

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• The bone marrow microenvironment protects B-cell precursor acute lymphoblastic leukemia (pre-B ALL) cells from drug therapies.
• Molecular mechanisms of this microenvironment-mediated protection are not fully understood.
• Galectin-3 (Lgals3) is a lectin found in various cellular locations.

Purpose of the Study:

• To investigate the role of Galectin-3 in the protective interactions between pre-B ALL cells and bone marrow stromal cells.
• To determine the source and mechanism of Galectin-3 uptake by ALL cells.
• To explore Galectin-3 as a potential therapeutic target against drug-resistant pre-B ALL.

Main Methods:

• Co-culture of pre-B ALL cells with bone marrow stromal cells.
• Analysis of Galectin-3 expression, localization, and secretion using immunofluorescence, Western blotting, and ELISA.
• Assessment of Galectin-3 internalization and its effect on ALL cell drug sensitivity and gene transcription.
• Investigation of the NF-κB pathway activation.

Main Results:

• Stromal cells, not ALL cells, are the primary source of Galectin-3 in co-cultures, secreting it and displaying it on their surface.
• ALL cells internalize stromal Galectin-3, which then stimulates endogenous LGALS3 mRNA transcription.
• Drug-tolerant ALL cells exhibit increased Galectin-3 levels, correlating with induced Galectin-3 transcription.
• Stromal Galectin-3 promotes ALL cell drug resistance, potentially via auto-induction of Galectin-3 and NF-κB pathway activation.

Conclusions:

• Stromal Galectin-3 plays a critical role in protecting pre-B ALL cells from drug treatment.
• Internalization of stromal Galectin-3 leads to increased endogenous Galectin-3 production in ALL cells, enhancing drug resistance.
• Targeting Galectin-3 presents a potential strategy to overcome the protective effects of the bone marrow microenvironment in pre-B ALL.