The Fusion Genes and Their Relation with Genetic Variants in Egyptian AML Patients

Abo Elwafa, Reham Abdel Haleem; ElBordiny, Magdy Mamdouh; Deghedy, Akram; Elghandour, Ashraf; Ammar, Engy Taher

doi:10.31557/APJCP.2025.26.3.1069

The Fusion Genes and Their Relation with Genetic Variants in Egyptian AML Patients

Document Type : Research Articles

Authors

¹ Clinical and Chemical Pathology Department, Alexandria University, Alexandria, Egypt.

² Hematology Unit, Internal Medicine Department, Alexandria University, Alexandria, Egypt.

10.31557/APJCP.2025.26.3.1069

Abstract

Background: Acute myeloid leukemia (AML) is a clonal malignant disorder of the bone marrow. Genetic aberrations have an unequivocal role in disease pathogenesis. With the application of next-generation sequencing technologies (NGS), an enormous number of genetic fusions and variants has been detected. Their co-occurrence has an impact on patient`s prognosis. Therefore, our aim in this study was to survey fusion genes as well as their relation with genetic variants. Subjects and methods: Targeted sequencing of the following fusion genes, in bone marrow aspirate samples, was performed; MECOM, MET, MLLT10, MLLT3, MYBL1, MYH11 and NTRK3. In addition sequencing for the hot spot regions in the following genes was done: FLT3, KIT, NRAS, KRAS, HRAS, using OncomineTM myeloid research panel on Ion S5 NGS system. The study was conducted on 24 denovo Egyptian AML patients of both sexes. Results: We identified one fusion in MYH11 gene (CBFB::MYH11) in two cases with four fusion transcripts of rare types. In addition, one novel breakpoint in MYH11 gene was identified. Also, about 337 variants in five genes were detected in all patients. Majority of them were benign. In the two positive cases for fusion; three pathogenic variants (2 KRAS, 1 NRAS), and one not-reported variant in FLT3 were reported. Conclusions: NGS has a major role in detection of genetic variants and fusions, which will have an impact on AML patient’s prognosis.

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