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

Intra-tumor heterogeneity impacts disease progression and therapeutic
resistance but remains poorly characterized by conventional histologic,
immunophenotypic, and molecular approaches. Single-cell biophysical
properties distinguish functional phenotypes complementary to these
approaches, providing additional insight into cellular diversity. Here, we
link both buoyant mass and stiffness to gene expression to identify
clinically relevant phenotypes within primary mantle cell lymphoma (MCL)
cells, employing MCL as a model of biological and clinical diversity in
human cancer. Linked measurements reveal that buoyant mass and stiffness
characterize B-cell development states from naïve to plasma cell and
correlate with expression of oncogenic B-cell receptor signaling genes
such as BLK and CD79A. Additionally, changes in cell buoyant mass within
primary patient specimens ex vivo correlate with sensitivity to
Bruton's Tyrosine Kinase inhibitors in vivo in MCL and chronic
lymphocytic leukemia, another B-cell malignancy. These findings highlight
the value of biophysical properties as biomarkers of response in pursuit
of future precision therapeutic strategies.