Exploring the Molecular and Microenvironmental factors in Risk of monoclonal Gammopathy Evolution (EMERGE)

Research summary

Myeloma is a treatable, but incurable, malignancy of plasma cells in the bone marrow (BM). It represents the final stage in a continuum of plasma cell disorders (PCDs) and is consistently preceded by a premalignant phase termed monoclonal gammopathy of undetermined significance (MGUS). MGUS therefore provides the opportunity to study how a premalignant condition progresses into cancer. MGUS-to-myeloma progression requires multiple genomic events and establishment of a permissive bone marrow microenvironment (BME). Historically, obtaining patient material to study MGUS has been challenging. This is because MGUS screening is unavailable, therefore most affected individuals are unaware they have MGUS. Furthermore, MGUS cells are rare and reside within the BM and thus can only be obtained by an invasive biopsy procedure which is not routinely performed in early-stage PCDs. This study is designed to provide a robust framework for collection of clinical information, patient samples and their subsequent analysis. Patients awaiting a total hip replacement will be invited to participate and consent sought to collect blood, bone marrow and bone tissue during surgery. At routine preoperative assessments, additional blood will be taken to screen for the presence of a monoclonal antibody, also known as a paraprotein, which is a marker of MGUS and other PCDs. Samples from patients without a paraprotein will act as a control source of blood and BM cells. We will apply cutting-edge techniques on samples collected to study the significance of early genomic events in mutant plasma cells, the associated changes in the epigenome, transcriptome and proteome, and characterize the BME in precursor disease states. Thus, we aim to further our understanding of precursor disease leading to progression to myeloma, with the hope of identifying biomarkers that can more accurately quantify individual risk for progression and set the stage for early interventions with novel therapies in the future.

Principal Investigator

Mr Antony Palmer

Contact us

Email: gail.lang@ndorms.ox.ac.uk

IRAS number

346267