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

Raed Alserihi, Hameeda Ahmad, Heba Alkhatabi, Talal Qadah, Shahad W. Kattan, Elrashed B. Yasin, Haitham M. H. Qutob, Waleed M. Bawazir, Abeer Fakhr-Eldeen, Manal S. Fawzy, Ahmad S. Barefah

International Journal of Biomedicine. 2023;13(1):73-83.
DOI: 10.21103/Article13(1)_OA9
Originally published March 3, 2023


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) (170bp and 330bp)  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 81.3×103/µL. 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 of NPM1/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.

acute myeloid leukemia • FLT3 • NPM1• sequencing
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Received December 13, 2022.
Accepted January 24, 2023.
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