Abstract
BackgroundRecognition 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.ObjectiveThis 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.MethodsThe 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.ResultsThe 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.ConclusionFLT3-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.
Highlights
Over the past decade, the field of acute myeloid leukaemia (AML) diagnostics has shifted from a primarily clinicopathological assessment to an integrated approach, including morphology, immunophenotyping, cytogenetics, and molecular genetics.[1,2] In an era of precision medicine, the use of molecular genetic data, in particular, has fundamentally shaped the diagnostic approach to patients with AML.[3]
This study investigated the presence and molecular characteristics of the nucleophosmin protein-1 (NPM1) and FLT3-internal tandem duplication (ITD) mutations in a newly diagnosed AML population in central South Africa
Acute myeloid leukaemia subtypes in our patient cohort comprised of AML with recurrent genetic abnormalities, AML with myelodysplasia-related changes, and AML not otherwise specified
Summary
The field of acute myeloid leukaemia (AML) diagnostics has shifted from a primarily clinicopathological assessment to an integrated approach, including morphology, immunophenotyping, cytogenetics, and molecular genetics.[1,2] In an era of precision medicine, the use of molecular genetic data, in particular, has fundamentally shaped the diagnostic approach to patients with AML.[3] Genetic profiling has led to more accurate diagnostic classification and improved risk stratification and identification of potential therapeutic targets.[1] Acute myeloid leukaemia is a genetically heterogeneous disease.[2] Recurrent structural chromosomal aberrations detected by conventional cytogenetics were previously considered the most relevant prognostic variable in addition to the patient’s age and performance status.[2,3] Three main cytogenetic risk groups (low, intermediate, and high) were defined, with approximately 50% of patients having a normal karyotype and falling into the intermediate cytogenetic risk group.[3,4]. 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
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