Analysis of NPM1 and FLT3 Mutations in Patients with Acute Myeloid Leukemia in Jeddah, Saudi Arabia: A Pilot Study

Background: The outcome of acute myeloid leukemia (AML) is influenced by ethnicity, geographic variations, and the patient's molecular profile. We aimed to explore the mutation frequencies of the nucleophosmin 1 (NPM1) and the FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) or tyrosine kinase domain (TKD) with correlation to the cytogenetic profiles in patients with AML.Methods and Results: Bone marrow/whole blood samples from 33 patients with AML were screened for NPM1/FLT3-ITD mutations by fragments analysis using a GeneScan analyzer. Depending on the fragment size, the NPM1 and FLT3 wild type (Wt) (170 bp and 330 bp) vs. mutated (170/174 bp and 330/351 bp) alleles, respectively, can be distinguished. The allelic ratio of FLT3-ITD+ was calculated. FLT3-TKD+ mutation was detected by Sanger sequencing. Samples were tested for chromosomal aberrations. According to the French-American-British (FAB) classification, the predominant type in the present cohort was AML-M5, accounting for 30.3%. NPM1+, FLT3-ITD+, and double mutations were found in 12.1%, 3.1%, and 6.1% of cases, respectively. The combined NPM1+/FLT3-ITD+/FLT3-TKD+ profile was presented in one patient (3.1%). The dual positivity group (NPM1+/FLT3+) significantly had a higher WBC count with a median of 81.3x103/mu L. A total of 63.6% of patients had abnormal cytogenetics. The NPM1+/FLT3-ITD+ patients had normal karyotypes. Patients with NPM1-/FLT3- showed complex karyotype (24%) and t(8;21) (8%). The FLT3-ITD+patient had trisomy 8.Conclusion: The frequency ofNPM1/FLT3 mutations in the study cohort showed less rate than in other studies with a distinct pattern. Due to the preliminary nature of the present work, more extensive screening is warranted to evaluate their usefulness as prognostic indicators in this region.

Automated summary

This study aimed to explore the mutation frequencies of NPM1 and FLT3 in patients with AML and their correlation with cytogenetic profiles. The study found different mutation types and cytogenetic abnormalities in the patients based on molecular analysis and chromosomal aberration testing. The frequency of NPM1/FLT3 mutations in this study cohort was lower and showed a distinct pattern compared to other studies. More extensive screening is required to evaluate their usefulness as prognostic indicators in this region.