Abo Elwafa Reham Abdel Haleem, ElBordiny Magdy Mamdouh, Deghedy Akram, Elghandour Ashraf, Ammar Engy Taher
Clinical and Chemical Pathology Department, Alexandria University, Alexandria, Egypt.
Hematology Unit, Internal Medicine Department, Alexandria University, Alexandria, Egypt.
Asian Pac J Cancer Prev. 2025 Mar 1;26(3):1069-1078. doi: 10.31557/APJCP.2025.26.3.1069.
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.
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.
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.
NGS has a major role in detection of genetic variants and fusions, which will have an impact on AML patient's prognosis.
急性髓系白血病（AML）是一种骨髓克隆性恶性疾病。基因畸变在疾病发病机制中具有明确作用。随着下一代测序技术（NGS）的应用，已检测到大量基因融合和变异。它们的共同出现会影响患者的预后。因此，我们本研究的目的是调查融合基因及其与基因变异的关系。
对骨髓穿刺样本中的以下融合基因进行靶向测序：MECOM、MET、MLLT10、MLLT3、MYBL1、MYH11和NTRK3。此外，使用Ion S5 NGS系统上的OncomineTM髓系研究面板对以下基因的热点区域进行测序：FLT3、KIT、NRAS、KRAS、HRAS。该研究对24例埃及初发性AML患者（男女均有）进行。
我们在2例患者中鉴定出MYH11基因中的1种融合（CBFB::MYH11），有4种罕见类型的融合转录本。此外，在MYH11基因中鉴定出1个新的断点。所有患者中还检测到5个基因中的约337个变异。其中大多数是良性的。在2例融合阳性病例中，报告了3个致病变异（2个KRAS、1个NRAS）以及1个FLT3中未报告的变异。
NGS在检测基因变异和融合方面具有重要作用，这将对AML患者的预后产生影响。
