A study of individuals with multiple myeloma (MM) revealed significant racial disparities in the prevalence of obesity and type 2 diabetes, and in the enrichment of a clock-like mutational signature among African American (AA) patients.
Emily Gallagher, MD, PhD, of Icahn School of Medicine at Mount Sinai, presented the data as a poster presentation at the 2021 American Society of Hematology (ASH) Annual Meeting.
Gallagher and colleagues used a large health system electronic medical record database to characterize the metabolic phenotype of AA patients and White patients with MM. The population included 3,170 patients; 21.7% were AA.
Obesity prevalence was highest in AA women (46%) followed by White men (41%), AA men (36%), and White women (35%). Prevalence for diabetes was greater in AA men (37%) and AA women (34%) compared with White men (24%) and White women (19%).
Genomic characterization of AA patients showed significant enrichment for the COSMIC SBS1 clock-like mutational signature in AA patients compared with White patients (P<.05). This was confirmed even after adjusting for age. This signature correlates with the age of individuals and may represent a cell division clock, Gallagher said.
In a mouse experiment, Gallagher and colleagues showed that MM xenografts more rapidly grew in diabetic mice and had more activation of the mTOR signaling pathway, which regulates clock and aging genes signatures. ON123300 was able to reverse the metabolic drive and directly reduce tumor growth in vivo xenograft models.