Multiple Myeloma

Proteomic profiling of Multiple Myeloma progression

Multiple myeloma (MM) is a malignant disorder characterised by the uncontrolled proliferation of plasma cells in the bone marrow. In nearly all patients, MM begins as Monoclonal Gammopathy of Undetermined Significance (MGUS), a premalignant condition with a low risk of progression to MM, though the risk persists throughout life. An intermediate clinical stage, Smouldering Multiple Myeloma (SMM), represents a transitional phase between MGUS and overt MM. At the time of MM diagnosis, patients typically present with significant organ damage, which serves as the key distinction between the asymptomatic stages (MGUS and SMM) and symptomatic MM.

Despite major advances in treatment, MM remains incurable, as most patients eventually experience relapse and develop resistance to therapy. While substantial genomic data are available across the disease spectrum, proteomic information remains limited, largely due to the complexity of clinical samples and the absence of reliable protein-based disease markers.

To address this gap, Dr Sushma Rao is leading a comprehensive plasma and bone marrow proteomics study using high-resolution mass spectrometry (HRMS) to analyse patient samples spanning the full spectrum of the disease from MGUS and SMM to active MM. Traditionally, MM diagnosis relies on bone marrow aspiration, an invasive and often painful procedure. In contrast, plasma provides a minimally invasive, readily accessible biological fluid, making it an attractive alternative for disease monitoring.

Across 2024/25, Dr Rao developed end-to-end workflows for plasma and marrow proteomics – covering sample processing, metadata standards, QC checkpoints and analysis pipelines – so they are ready for transfer upon commissioning of FECRI’s new Bruker timsTOF Pro2 integrated with ProteoElute. The facility will then support systematic profiling from MGUS and SMM through to active MM, accelerating biomarker discovery for disease monitoring.

By identifying previously unrecognised proteomic signatures linked to myeloma progression, this study seeks to provide valuable insights into cellular signalling pathways that would aid early detection and intervention. Ultimately, this research could pave the way toward less invasive diagnostic tools and a deeper understanding of how protein-level changes drive the pathogenesis of multiple myeloma.