Project Details
Description
PROJECT SUMMARY
Multiple myeloma (MM) is a devastating clonal plasma cell (cPC) malignancy responsible for over 13,000
deaths in the US per year. It is always preceded by pre-malignant, asymptomatic plasma cell disorders such as
monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM).
Despite the availability of various clinical, genomic, and imaging-based risk stratification models, accurate
classification of precursor cPC disorders and their risk of progression to MM remains elusive. The fundamental
roadblock remains in the inability of existing clinical and laboratory-based biomarkers to distinguish between
the presence of premalignant or malignant cPCs in patients. In contrast, recent advances in mass-
spectrometry based metabolomics offers new opportunities to characterize intra- and extracellular metabolites
that could serve as novel biomarkers reflective of the presence of malignant cPCs. This is especially promising
since oncogenic drivers of progression of premalignant to malignant cPCs, such as c-Myc, has known
downstream effects on multiple intracellular metabolic pathways resulting in altered extracellular metabolite
levels. These resultant metabolite profiles can be exploited to more accurately assess the risk of progression of
precursor cPC disorders to MM in the future and ultimately affect management and treatment. Thus, this
research proposal will test the hypothesis that the levels of select metabolites within the bone marrow (BM)
plasma are reflective of the qualitative and quantitative presence of c-Myc-activated malignant cPCs in patients
with PC disorders. This research proposal will specifically validate the presence of differences in the levels of
select metabolites in the BM plasma between MGUS and MM patients (Aim 1). It will also evaluate the effect of
c-Myc activation in cPCs on their extracellular levels of these select metabolites (Aim 2). Finally, it will evaluate
how depleting the malignant cPCs with systemic therapy affects the BM plasma levels of these select
metabolites in MM (Aim 3). These studies will provide an opportunity to advance our understanding of the
metabolic rewiring associated with the pathogenesis of MM. This could allow us to better determine the
transition from MGUS to symptomatic MM for the development of potential early diagnostic or preventative
strategies. The expertise and resources of the members of the team, the availability of the Myeloma SPORE
biobank and a NIH-designated comprehensive metabolomics core at the Mayo Clinic ensures the viability and
execution of the proposed experiments.
Status | Active |
---|---|
Effective start/end date | 3/1/21 → 2/28/25 |
Funding
- National Cancer Institute: $327,341.00
- National Cancer Institute: $356,438.00
- National Cancer Institute: $74,489.00
- National Cancer Institute: $327,341.00
Fingerprint
Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.