Integrative single-cell analysis reveals malignant archetypes and proliferative hierarchies in multiple myeloma [Part 4 of 4: Illumina NovaSeq X; MARS_v2]

Here, we present a population-level single-cell atlas of MM and detailed clinical annotations from 342 patients representing MM disease and treatment continuum. Our analysis identifies five distinct malignant transcriptional archetypes (MM1–MM5), and a proliferative module variably expressed across archetypes.

This proliferation signature emerges as a context-dependent program with independent prognostic value across archetypes. Combined archetype classification with proliferation scoring defines therapeutic resistance, genomic instability, and clinical outcomes. External validation using the CoMMpass cohort confirms the biological robustness and prognostic relevance of this stratification across platforms.