Integrating single-cell biophysical and transcriptomic features to resolve functional heterogeneity in mantle cell...

Area of Science:

• Biophysics
• Oncology
• Cell Biology

Background:

• Intratumor heterogeneity complicates cancer progression and treatment resistance.
• Conventional methods struggle to fully characterize cellular diversity.
• Single-cell biophysical properties offer complementary insights into functional phenotypes.

Purpose of the Study:

• To link single-cell biophysical properties (buoyant mass, stiffness) to gene expression in mantle cell lymphoma (MCL).
• To identify clinically relevant phenotypes within MCL cells.
• To explore the potential of biophysical properties as biomarkers for therapeutic response.

Main Methods:

• Linked measurements of buoyant mass, stiffness, and gene expression in MCL cells.
• Analysis of primary patient specimens ex vivo.
• Correlation of biophysical properties with sensitivity to Bruton's tyrosine kinase inhibitors.

Main Results:

• Buoyant mass and stiffness characterize B cell development states and correlate with oncogenic signaling genes (e.g., BLK, CD79A).
• Changes in cell buoyant mass in patient samples correlate with ex vivo sensitivity to Bruton's tyrosine kinase inhibitors.
• These biophysical properties are relevant in both mantle cell lymphoma and chronic lymphocytic leukemia.

Conclusions:

• Single-cell biophysical properties provide valuable biomarkers for understanding cancer heterogeneity.
• Buoyant mass and stiffness can predict response to targeted therapies like Bruton's tyrosine kinase inhibitors.
• Biophysical profiling holds promise for advancing precision therapeutic strategies in B cell malignancies.