||1R56CA272883-01 Interpret this number
||Mayo Clinic Rochester
||Differences in Tumor Biology of Multiple Myeloma in Association with African Ancestry
Multiple myeloma (MM) is a devastating and incurable plasma cell (PC) malignancy with ~30,000 new diagnoses
and ~12,000 deaths annually in the United States. Even though MM is the most common blood cancer in African
Americans (AAs), accounting for ~20% of overall cases, AAs have been significantly underrepresented in MM
research studies and clinical trials. MM has one of the most pronounced disparities in the incidence and mortality
between AAs and European Americans (EAs). Our group has shown that AAs are 2-3 times more likely to
develop MM with a 4-year younger age of onset compared to European Americans (EAs), even after adjusting
for socioeconomic factors. Moreover, AAs with MM currently have poorer disease survival compared with EAs.
Because MM research studies have largely focused on patients of European ancestry, it is unknown if the
disparities between AAs and EAs arise from differences in MM disease biology and/or tumor response to therapy.
A better understanding of the molecular mechanisms underlying MM in AAs and EAs will improve our knowledge
of the disease and have direct implications to the health disparity impacting AAs with MM.
Provided the wealth of studies on EAs, our long-term goal is to systematically characterize MM disease biology
and response to therapy focusing on MM patients of African ancestry. The objective of this proposal is to
characterize the genetic variations of the tumor and its tumor microenvironment (TME) and the impact of this
variation on response to therapy and disease survival in a large cohort of AA patients with MM. The rationale for
these investigations is strongly supported by our preliminary data. We hypothesize that AAs have differences in
MM tumor genetics that can lead to distinct responses to therapies. However, no large-scale studies comparing
MM tumor genetic variation, TME, response to therapy and disease survival among AA patients and calculated
ancestry have been done. The proposed studies will identify any racial differences in genetic variation of the
tumor (Aim 1) and TME (Aim 2) and in therapeutic responses (Aim 3) to assess overarching impacts to therapy
and disease survival. Understanding variables that impact response to therapy among AAs will be critical for
identification of optimal therapeutic strategies in this underserved population.