Abstract 3774: Genomic landscape of acute myeloid leukemia in an African ancestry cohort: A pilot study

Abstract Introduction: Acute myeloid leukemia (AML) is a diverse hematologic cancer that is distinguished by the uncontrolled growth and improper development of immature clonal myeloid cells. AML patients' age, performance status, comorbidities, genetics, and other clinical characteristics unique to leukemia, such as molecular classification, all influence their prognosis. Methods: In a pilot mixed African sample (Tanzania and Nigeria), we explore and identify genomic mutations and their possible influence on the clinical outcome of AML in an African Ancestry population. A total of six participants were recruited for the pilot study: n=4 (67%) from Tanzania and n=2 (33%) with an age range of between 14-71 years, and (2)33% female and (4)67% females. Genomic DNA was obtained from blood samples of all participants; a DNA library was prepared with targeted selected genes associated with Leukemia and sequenced on an Illumina Next-generation sequencer. Results: The study demonstrated numerous and diverse mutations in the African ancestry population. While CEBPA and BTK show 100% mutation, STAG2, CALR, BRAF, NOTCH1, and ZRSR2 demonstrated the lowest mutation (17%) in AML. A missense mutation predominates in CSF3R, NRAS, BRAF, ASXL1, BTK, and CBL, while CALR and NOTCH1 had only in-frame deletions. In-frame driver mutations were found in FLT3 AML_3, while FLT3 and NOTCH1 were found only in AML_4. All samples had a mutation in SETBP1, CEBPA, and BTK. Pathogenic mutations were detected with a frequency of 67% in FLT3, 33% in NRAS and 17% in BRAF, NOTCH1, and CALR. The NRAS mutations identified in this study have been associated with cancers other than AML and stand out in our cohort, as both genetic modifiers of AML biology and therapeutic targets. BRCA1 and TP53 are the most common pathogenic mutated variants in the TCGA dataset. They both show robust therapeutic targeting potential. Conclusions: The molecular signature identified in this African Ancestry population demonstrated genomic diversity in the African Ancestry population. Some of the genomic variations identified in this study are rarely documented in AML (NRAS; Gln61His, Gly13Asp: BRAF Val600Glu, Val640Glu). This is an indication of the need to review the genomic criteria for the diagnosis and management of AML, especially with more comprehensive data of the African Ancestry population. We describe various mutated genes with their potential therapeutic targets in AML, including DASATINIB (CBL), which shows promise as a therapeutic target for AML in the African Ancestry population. This study provides a basis for committing resources to a larger cohort and further exploring the genomic diversity and variants in an African Ancestry population. Citation Format: Oluyemi Akinloye, Olayiwola Akianji Popoola, Olatunde Fakoya, Stella Rwazuala, Nneka Nwanyiaru Osobukola, Michael Forster. Genomic landscape of acute myeloid leukemia in an African ancestry cohort: A pilot study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3774.