Ancestry-associated social and genomic hallmarks linked with inferior outcome in elderly acute myeloid leukemia

Recent literature reports inferior outcomes for patients of African ancestry (AA) who develop acute myeloid leukemia (AML). We herein present a cohort of 396 patients with 116 patients of AA (29%) who show inferior survival outcomes for patients of African ancestry ≥ 60 years (p = 0.008). Our cohort also demonstrated significantly increased rates of monosomy 7 and 7q deletions in the patients of AA (p = 0.04, p = 0.03), suggesting association with genomic instability and loss of chromatin stabilization protein EZH2, DNA repair function mediated by CUX1, and SAMD9L anti-proliferation effect. Increased genomic instability may be mediated by accelerated aging related to environmental stressors or inherited genomic patterns. We also assessed the influence of neighborhood vulnerability. Patients of AA were more likely to live in census tracts with more people living below the 150% poverty level (p < 0.01). Undergoing allogeneic hematopoietic cellular transplant (allo-HCT) provided improved outcomes to patients of AA, highlighting the need to optimize access and supportive care for allo-HCT for minority patients. In multivariate analysis, race was not retained as an independent predictor of survival. Instead, adverse ELN22 risk and higher socioeconomic vulnerability scores were independently associated with inferior outcomes. These findings suggest that disparities in survival may be largely driven by the intersection of biological risk and social determinants of health, rather than ancestry itself acting as an independent prognostic factor.