Multiple myeloma (MM) is a cancer of bone marrow plasma cells that results in over ten thousand deaths a year in the USA.It is always preceded by a pre-malignant phase called monoclonal gammopathy of undetermined significance (MGUS). MGUS is very common (4% of adults), and overall has a low risk (~1-2%) each year of progressing to MM. We are unable to prevent the progression to MM, and currently recommend that patients with MGUS be followed annually. Unfortunately most patients progress to MM between the annual visits, sufferring from the complications of MM that include bony disease, anemia, and renal insufficiency. Most of the genetic changes identified in MM are also present in MGUS, however recently we have identified candidate genetic mutations that may drive the progression of MGUS to MM, potentially providing a useful genetic biomarker. This project will explore the genetic differences between patients with MGUS and MM with the goal of understanding the genetic mechanisms of progression and improving our risk prediction models, and preventing MGUS patients from suffering the complications of MM.

Public Health Relevance

Monoclonal gammopathy of Undetermined Significance is a very common condition, affecting 4% of adults, that can lead at a a low rate to multiple myeloma, an incurable malignancy that causes bone destruction, anemia and renal insuffiency. We will identify genetic mutations associated with the progression so that we can pre-emptively identify the patients at greatest risk, and seek to prevent the complications of myeloma.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA195688-03
Application #
9384987
Study Section
Cancer Biomarkers Study Section (CBSS)
Program Officer
Sorbara, Lynn R
Project Start
2015-12-11
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Mayo Clinic, Arizona
Department
Type
DUNS #
153665211
City
Scottsdale
State
AZ
Country
United States
Zip Code
85259
Calcinotto, Arianna; Brevi, Arianna; Chesi, Marta et al. (2018) Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression. Nat Commun 9:4832
Demchenko, Yulia; Roschke, Anna; Chen, Wei-Dong et al. (2016) Frequent occurrence of large duplications at reciprocal genomic rearrangement breakpoints in multiple myeloma and other tumors. Nucleic Acids Res 44:8189-98