A global study led by researchers at The Ohio State University Comprehensive Cancer Center has identified critical molecular predictors of survival in Black patients diagnosed with acute myeloid leukemia (AML). The findings, published in Nature Genetics, suggest that current AML risk stratification models should be modified to include ancestry-specific genetic factors, and that these factors should be tested in clinical trials to improve outcomes for this underserved population.
Ann-Kathrin Eisfeld, MD, director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at OSUCCC—James, emphasized the importance of diversity in clinical studies, stating, "There is so much knowledge and improvement in care to be gained for all our patients if we strive toward inclusivity in our efforts. This study is just the first of many steps needed."
Disparities in AML Genomic Data
The study highlights a significant disparity in AML genomic data, with Black patients historically underrepresented in genomic studies. While Black patients represent 9% of AML diagnoses, they account for less than 2% of patients in most cancer genomics-based discovery studies. This underrepresentation leads to inequitable application of molecular medicine and potentially inadequate treatment strategies, contributing to inferior outcomes for Black patients with AML.
Elaine Mardis, Ph.D., co-executive director of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children's Hospital, noted, "The results we've reported are striking and emphasize the role genomics can play in identifying ancestry-specific aspects of cancer onset and outcomes."
Key Findings: Mutation Frequencies and Survival
The researchers compared genetic mutation frequencies in 100 Black patients with AML to those of 323 white patients. The analysis revealed that 73% of 162 gene mutations recurrent in Black patients were either found in only one white patient or not detected at all. Specifically, mutations in NPM1 and NRAS genes were associated with inferior disease-free survival in Black patients, while mutations in IDH1 and IDH2 genes were linked to reduced overall survival.
Furthermore, the study found differences in inflammatory profiles, cell-type distributions, and transcriptional profiles between Black and white patients with NPM1 mutations.
Impact on Risk Stratification
Incorporating these ancestry-specific mutations into the European Leukemia Net (ELN) genetic risk stratification system resulted in a change in risk group assignment for one-third of Black patients, ultimately improving the accuracy of outcome predictions. This suggests that tailoring risk assessment based on genetic ancestry could lead to more personalized and effective treatment strategies.
Future Directions
The researchers advocate for genomic profiling of additional Black AML samples to validate these initial findings. They also emphasize the need for a conclusive clinical trial to change AML risk stratification based on genetic ancestry. Electra Paskett, Ph.D., deputy director for population sciences and community outreach at the OSUCCC—James, highlighted the importance of including diverse participants in biobanking studies to assess genomic factors across race.
Eisfeld and Mardis hope that this study will serve as a precedent for future genomic profiling efforts, addressing the current underrepresentation of historically marginalized patient populations and improving the understanding of AML biology.
