Project Details
Description
PROJECT SUMMARY/ABSTRACT
Multiple myeloma (MM) is a life-threatening plasma cell malignancy. It is 2-3 times more common in blacks
compared with whites. MM has a prolonged clinically detectable premalignant phase called monoclonal
gammopathy of undetermined significance (MGUS) that can be identified by detection of the secreted
monoclonal immunoglobulin (commonly referred to as a monoclonal protein). MM is a serious incurable
malignancy, and the best approach for treatment is to prevent end organ damage by early intervention. This is
best done by targeting patients with an intermediate asymptomatic stage referred to as smoldering multiple
myeloma (SMM) that resides between MGUS and MM. Over the last 5 years of this grant we have extensively
investigated the reasons why MM is more common in blacks compared with whites, demonstrated that first-
degree relatives of patients with MM have a high risk of having the precursor MGUS lesion, and identified
several biomarkers that predict risk of imminent progression in SMM. Our studies show that a principal reason
for high risk of MM in African Americans is that they have a high risk of the precursor MGUS condition, which
we also found is present at a much earlier in age in blacks compared with whites. More recently we made an
important discovery using DNA sequencing based ancestry analysis that 3 specific cytogenetic abnormalities in
MM account for most of the racial disparity. Our research has assumed greater urgency with recent findings
that early intervention (in high-risk SMM stage) can prevent end-organ damage and prolong overall survival.
The goals of this renewal are to further determine the mechanisms behind the racial disparity in incidence of
MM, to identify new biomarkers for high risk SMM needing therapy, and to develop a feasible screening
strategy to identify patients with SMM. In Aim 1 we will determine the age at onset of MGUS using sensitive,
mass spectrometry (MS)-based detection of monoclonal protein in >12,000 NHANES samples, and identify
new cytogenetic abnormalities that are associated with predisposition to MM in blacks. In Aim 2 we will identify
new biomarkers that are associated with high risk of progression from SMM to symptomatic MM, specifically
utilizing mass spectroscopic characterization of the monoclonal protein, measurement of circulating clonal
plasma cells, and by studying clonal diversity and immune profile. In Aim 3, we will institute and determine the
feasibility and impact of a screening approach for identification of SMM eligible for early intervention, by
targeting high risk populations, specifically African Americans, first-degree relatives, and persons with high
total protein levels. Our grant will have a major impact on the management of patients with SMM and MM,
especially African Americans and first-degree relatives or persons with MM.
Status | Active |
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Effective start/end date | 7/17/12 → 6/30/24 |
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