Genomic Landscape of Acute Myeloid Leukemia in a mixed African Cohort: A Pilot Study

Background 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 population. A total of six participants was recruited for the pilot study: n = 4 (67%) from Tanzania and n = 2 (33%) with an age range of between 14–71 years and 33% female and 67% females. Genomic DNA was obtained from blood samples of all participants, DNA library was prepared with targeted selected genes associated with Leukemia and the Library sequenced on Illumina Next generation sequencer. Results 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 target. Other genes identified include IDH1, CEBPA, CSF3R, PLCG2, BTK, CBL, DDX41 and SETBP1 but had less clinical relevance in AML. Conclusions The molecular signature identified in this cohort is associated with the genomic diversity in Africans and could be linked to the variability in treatment outcomes and molecular classification of AML. This study provides a basis to commit resource to a larger African study in AML and to further explore the genomics diversity and variance in an indigenous African population.