Deep Visual Proteomics Unveils Precision Medicine Insights in Composite Small Lymphocytic and Classical Hodgkin Lymphoma

Abstract

Coexistence of two cancer types in the same organ presents challenges for clinical decision-making, calling for personalized treatment strategies. Deep Visual Proteomics (DVP) combines AI driven single cell type analysis with laser microdissection and ultrasensitive mass spectrometry. In a composite case of classical Hodgkin lymphoma (cHL) and small lymphocytic lymphoma (SLL) in a single patient, we investigated the potential of DVP to inform precision oncology. We quantified the proteomic landscapes in the cHL and SLL to a depth of thousands of proteins. Our analysis revealed distinct proteome profiles in cHL and SLL populations, highlighting their clonal unrelatedness. Our data suggested standardized chemotherapy and interleukin-4 inhibition as potential strategies to manage chemo-resistance – instead of bone marrow transplantation. DVP highlighted minichromosome maintenance protein and proteasome inhibitors for cHL and H3K27 methylation and receptor tyrosine kinase inhibitors for SLL as subtype-specific treatments. Thus cell-type specific insights of DVP can guide personalized oncological treatments.