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Grant Details

Grant Number: 1R56CA272883-01 Interpret this number
Primary Investigator: Baughn, Linda
Organization: Mayo Clinic Rochester
Project Title: Differences in Tumor Biology of Multiple Myeloma in Association with African Ancestry
Fiscal Year: 2022


Abstract

PROJECT SUMMARY 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.



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