Abstract IA003: Integrated consideration of constitutional and somatic genetic features to improve knowledge and care of AML patients

Abstract Our knowledge of the genomics of acute myeloid leukemia (AML), which serves as the basis of clinically used prognostic biomarkers and therapeutic advances (including targeted therapies), is almost exclusively based on data from patients of European ancestry. However, recent research efforts uncovered differences in somatic mutation frequencies in AML patients with respect to genetic ancestry, as well as differences in their previously established prognostic impact when referring to response to standard of care chemotherapy. Together, this strongly suggests the importance to consider differences in the constitutional genetic background and their direct or indirect effects on somatic genomic features. We will discuss interconnected contributors to survival disparities especially of non Hispanic (NH)-Black patients with AML, highlighting social contributors, trial enrollment and structural racism. We will highlight the diverse genetic and genomic landscape of patients with AML, including the identification of several recurrent gene mutations thus far not established in AML identified in NH-Black patients. We will highlight differences in immune response patterns that may affect the observed phenotypes, including both coding and non-coding RNAs. Importantly, we will show examples of how this new information derived from a more inclusive patient population is able to refine the disease biology of all AML patients. Lastly, there will be insights into differential prognostic impact of gene mutations, including biologic rationales for the observed ancestry-associated effects via comprehensive, multi-omic single cell sequencing studies; that strongly suggest the need to consider genetic ancestry in clinically used prognostic risk assignments. Citation Format: Ann-Kathrin Eisfeld. Integrated consideration of constitutional and somatic genetic features to improve knowledge and care of AML patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr IA003.