The genetic landscape of acute myeloid leukaemia in the South African public sector

Abstract

Background: Acute myeloid leukaemia (AML) is a heterogeneous group of myeloid neoplasms for which two international classification systems exist: the 2022 World Health Organization (WHO) and international consensus classification of myeloid neoplasms (ICC), with an emphasis on molecular abnormalities. Aim: To determine the molecular-genetic profile of AML in the South African public sector. Setting: The Charlotte Maxeke Johannesburg Academic Hospital, Somatic Cell Genetics Unit, National Health Laboratory Service, South Africa. Methods: All newly diagnosed AML cases analysed with next generation sequencing (NGS) between January 2019 and December 2022 were retrospectively reviewed. Clinical and laboratory data were obtained from the laboratory information system. Results: In total, 194 AML cases were tested by NGS (162 classifiable), with a median age of 42 years for adults and 7 years for the paediatric cohort. There were 21 cases of AML with mutated TP53 (ICC), 5 of which were unclassifiable with the WHO classification system. In t(8;21) (q22;q22.1), KIT and FLT3-ITD mutations were present in 43% and 20% of cases respectively; FLT3-ITD in 50% of acute promyelocytic leukaemia (APL) and ~20% of AML with NPM1 were triple mutated (NPM1, DNMT3A, FLT3-ITD). Conclusion: This study revealed a high proportion of exon 17 KIT mutations in t(8;21), FLT3-ITD mutations in APL and triple mutated AML with mutated NPM1, all of which are likely to be driving the poor outcomes seen in these AML subgroups in our setting. Contribution: This is the first nationwide description of the molecular-genetic landscape of AML in the South African public sector.

Keywords

• acute myeloid leukaemia
• south africa
• next generation sequencing
• european leukaemianet
• international consensus classification
• world health organization