Multiomic profiling identifies predictors of survival in African American patients with acute myeloid leukemia

Area of Science:

• Genomics
• Hematology
• Cancer Research

Background:

• Genomic profiles and prognostic biomarkers in acute myeloid leukemia (AML) are underexplored in diverse populations.
• Limited data exists on genetic variations and their impact on AML outcomes in patients of African ancestry.

Purpose of the Study:

• To analyze genomic profiles and identify prognostic biomarkers in Black patients with AML.
• To compare mutation frequencies between Black and white patients with AML.
• To evaluate the impact of ancestry-specific markers on risk stratification and outcome prediction.

Main Methods:

• Exome and transcriptome analysis of 100 Black patients with AML (Alliance cohort).
• Comparison of somatic mutation frequencies with 323 white patients with AML (BeatAML cohort).
• Multivariable analyses to identify prognostic markers and assess risk stratification.

Main Results:

• 73% of gene mutations recurrent in Black patients were rare or absent in white patients.
• A novel PHIP alteration was identified in 7% of Black patients.
• NPM1 and NRAS mutations correlated with inferior disease-free survival; IDH1/IDH2 mutations with reduced overall survival in Black patients.
• Significant differences in inflammatory profiles, cell types, and transcriptional profiles were observed between Black and white patients with NPM1 mutations.
• Ancestry-specific risk markers altered risk group assignment for one-third of Black patients, improving outcome prediction.

Conclusions:

• Genomic landscapes of AML differ significantly across ancestral backgrounds.
• Ancestry-specific prognostic markers are crucial for accurate risk stratification and improved outcome prediction in AML.
• Further research into the unique biological and clinical characteristics of AML in diverse populations is warranted.