Original Research

Molecular characterisation of NPM1 and FLT3-ITD mutations in a central South African adult de novo acute myeloid leukaemia cohort

Jean F. Kloppers, André de Kock, Johané Cronjé, Anne-Cecilia van Marle
African Journal of Laboratory Medicine | Vol 10, No 1 | a1363 | DOI: https://doi.org/10.4102/ajlm.v10i1.1363 | © 2021 Jean Kloppers, Anne-Cecilia van Marle, Johané Cronjé, André de Kock | This work is licensed under CC Attribution 4.0
Submitted: 17 August 2020 | Published: 30 June 2021

About the author(s)

Jean F. Kloppers, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; and, Department of Haematology and Cell Biology, Universitas Academic Unit, National Health Laboratory Services, Bloemfontein, South Africa
André de Kock, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; and, Department of Haematology and Cell Biology, Universitas Academic Unit, National Health Laboratory Services, Bloemfontein, South Africa
Johané Cronjé, Department of Haematology and Cell Biology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; and, Department of Haematology and Cell Biology, Universitas Academic Unit, National Health Laboratory Services, Bloemfontein, South Africa
Anne-Cecilia van Marle, Department of Haematology and Cell Biology, School of Pathology, Faculty of Health Sciences, University of the Free State, Bloemfontein, South Africa; and, Department of Haematology and Cell Biology, Universitas Academic Unit, National Health Laboratory Services, Bloemfontein, South Africa


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Abstract

Background: Recognition of molecular abnormalities in acute myeloid leukaemia (AML) has improved our understanding of its biology. NPM1 and FLT3-ITD mutations are recurrent in AML and clinically significant. NPM1 mutations are associated with a favourable prognosis, while FLT3-ITD mutations are an independent poor prognostic factor in AML.

Objective: This study described the prevalence and molecular characteristics of the NPM1 and FLT3-ITD mutations in a newly diagnosed AML patient cohort in central South Africa.

Methods: The study included 40 de novo AML patients. An NPM1 and FLT3-ITD multiplex polymerase chain reaction assay was optimised to screen patients for the respective mutations and were confirmed using Sanger sequencing. The prevalence of the NPM1 and FLT3-ITD mutations were determined, and mutation-specific characteristics were described in relation to patients’ demographic information and AML classifications.

Results: The patients’ median age was 38.5 years, with 77.5% (n = 31) of patients being self-proclaimed Black Africans. AML with recurrent genetic abnormalities was most prevalent (57.5%; n = 23), of which acute promyelocytic leukaemia (APL) was most common (40.0%; n = 16). None of the patients had the NPM1 mutation. FLT3-ITD was present in 37.5% (6/16) of APL patients and in one (20.0%) of five AML patients with a t(8;21) translocation. Most patients had an FLT3-ITD allele ratio of ≥ 50% and ITD lengths of > 39 bp.

Conclusion: FLT3-ITD mutations were mainly found in APL cases at a similar prevalence as reported in the literature. High FLT3-ITD allele ratios and long ITD lengths predominated. No NPM1 mutations were detected.


Keywords

acute myeloid leukaemia; AML; NPM1; FLT3-ITD; frequency; South Africa

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