Identifying Ancestry-Based Predictors of Survival in Black Patients with Acute Myeloid Leukemia

Researchers use multiomic profiling to understand ancestry-specific aspects of cancer onset and outcomes.

In a recent study, published in ­­­Nature Genetics, researchers from Nationwide Children’s Hospital and The Ohio State University Comprehensive Cancer Center (OSUCCC – James) compared genomic profiles of patients diagnosed with AML having self-reported and genomically-confirmed African ancestry and to patients diagnosed with AML who self-reported White and had genomically confirmed European ancestry. All patients studied were similarly treated on Alliance cooperative group clinical trials and had known disease outcomes. Co-corresponding authors for the study are Ann-Kathrin Eisfeld, MD, director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at the OSUCC – James, and Elaine Mardis, PhD, co-executive director of the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital.

AML is a quickly progressing cancer of the blood and bone marrow.  Currently, there is a limited understanding of genomic profiles and the biomarkers that help predict outcomes and determine treatment plans for acute myeloid leukemia (AML) in people of diverse ancestral backgrounds.

Previous studies have shown that Black patients with AML have unfavorable outcomes when compared with white patients, even when receiving similar clinical treatment for their disease. This disparity may be due to the differences in the underlying DNA profiles of gene mutations between ancestry-diverse populations. This gap increases the potential for inadequate treatment and often results in poor disease outcomes. For molecular medicine to truly be effective, there must be a diverse database to reference, says Dr. Mardis.

The research team found that 73% of the 162 gene mutations identified in multiple Black patients were found in fewer than 1% of White patients. They also identified several new genes with recurrent mutations in 4-7% of Black patients that had not been previously reported occur in AML.

When ancestry-specific risk markers from this study were incorporated into the 2022 European LeukemiaNet genetic-risk stratification that is clinically used to evaluate AML patients and establish their treatment approach, the assigned risk assessment for 33% of Black patients changed and their outcome predictions improved.

“The results we have reported are striking and emphasize the role that genomics can play in identifying ancestry-specific aspects of cancer onset and outcomes,” says Dr. Mardis, who is also co-leader of the OSUCCC – James Translational Therapeutics Program.

The study also found that Black patients with myelodysplastic syndrome, a condition that can lead to AML onset were younger on average than White patients with this diagnosis. This result suggests that some stressor among this group influences myelodysplasia.

“Perhaps the most important thing for providers to know is that the ‘normal rules do not apply’ for interpreting test results from a clinical genomics-based comparison of tumor and matched normal tissue DNA in minoritized AML patients,” says Dr. Mardis. “While we haven’t yet adopted a different prognosis approach for Black patients, the current European Leukemia Net guidelines, based on our results, appear to be not appropriate for determining care in these individuals.”

Though these initial results from the study are intriguing, further genomic profiling of additional Black AML samples will be required, which is currently underway. To change AML risk stratification based on genetic ancestry, a conclusive clinical trial will need to be conducted.

References:

Stiff A, Fornerod M, Kain B.N., et al. Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia. Nature Genetics. 2024. DOI: 10.1038/s41588-024-01929-x

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