Longitudinal single-cell analysis of a myeloma mouse model identifies subclonal molecular programs associated with progression.

ABSTRACT: Molecular programs that underlie precursor progression in multiple myeloma are incompletely understood. Here, we report a disease spectrum-spanning, single-cell analysis of the Vκ*MYC myeloma mouse model. Using samples obtained from mice with serologically undetectable disease, we identify malignant cells as early as 30 weeks of age and show that these tumours contain subclonal copy number variations that persist throughout progression. We detect intratumoural heterogeneity driven by transcriptional variability during active disease and show that subclonal expression programs are enriched at different times throughout early disease. We then show how one subclonal program related to GCN2 stress response is progressively activated during progression in myeloma patients. Finally, we use chemi

SUBMITTER: Croucher DC 

PROVIDER: S-EPMC8566524 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature