Targeted mutational profiling of Fms-like tyrosine kinase 3, nucleophosmin 1, and isocitrate dehydrogenase 2 in acute myeloid leukemia: Associations with remission, subtypes, and survival

Abstract

Acute myeloid leukemia is a genetically heterogeneous disease in which genetic alterations play a key role for diagnosis, prognosis, and therapy options. Fms-Like Tyrosine Kinase 3 (FLT3), Nucleophosmin 1 (NPM1), and isocitrate dehydrogenase 2 (IDH2) mutations have clinical significance by influencing the biological features and treatment outcomes. The aim of this study was to characterize the mutational profile of FLT3, NPM1, and IDH2 in acute myeloid leukemia (AML) patients and determine their association with remission status, AML subtypes, and overall survival (OS). A prospective longitudinal study was performed on 40 newly diagnosed AML patients. The responses for 21 patients were monitored after induction chemotherapy. Bone marrow and blood samples were collected and genomic DNA was extracted. FLT3-internal tandem duplication and FLT3-TKD and of NPM1 and IDH2 mutations analyzed by the polymerase chain reaction followed by Sanger sequencing. Survival rate was assessed using the Kaplan–Meier approach for OS. The molecular heterogeneity of AML is reflected by the most commonly observed mutations: Overall NPM1 mutations (100% of cases possesses various mutations), followed by FLT3 (25%) and IDH2 (7.5%). Remission rates for patients with a single gene mutation or wild-type FLT3 were greater than those with co-occurring mutations/FLT3 mutations. While NPM1 mutations, particularly exon 11 insertions and duplications, were associated with favorable outcomes, NPM1 “deletions” were observed in only 62.5% of cases and exhibit a clear pathogenic role. OS analysis showed no significant differences in survival between FLT3 mutation and NPM1 mutation groups. These results support clinical significance of FLT3, NPM1, and IDH2 mutations in AML and highlight the potential role of these genes in targeted therapy considerations.