Identify high-risk disease in multiple myeloma through single cell detection of highly proliferative (PR) cells

Description

This project investigates the biological and microenvironmental mechanisms that drive the development of highly proliferative (PR) subclones in patients with newly diagnosed multiple myeloma. Preliminary data from a single-cell analysis indicate that PR subclones are prevalent at relapse, predict shorter progression-free survival, and proliferate under treatment pressure. The first aim is to define the transcriptomic signature of PR subclones in 120 newly diagnosed patients lacking conventional high-risk features and to functionally validate key genes. The second aim will determine how treatment-induced remodeling of the bone marrow immune microenvironment promotes PR subclones persistence and expansion by leveraging paired tumor-immune single-cell datasets from 40 patients in the MIDAS study. Ultimately, this project will refine the definition of high-risk multiple myeloma and open new avenues for developing new therapeutics and improving patient outcomes.