Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion
Introduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of immature myeloid cells. Among the genetic alterations in AML, the RUNX1- RUNX1T1 fusion, resulting from the t (8; 21) (q22; q22.1) translocation, is common and linked with a f...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Alexandria Journal of Medicine |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/20905068.2024.2387881 |
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| author | Magdy Elbordiny Reham AboElwafa Abeer Elhadidi Ashraf Elghandour Salma Elmasry |
| author_facet | Magdy Elbordiny Reham AboElwafa Abeer Elhadidi Ashraf Elghandour Salma Elmasry |
| author_sort | Magdy Elbordiny |
| collection | DOAJ |
| description | Introduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of immature myeloid cells. Among the genetic alterations in AML, the RUNX1- RUNX1T1 fusion, resulting from the t (8; 21) (q22; q22.1) translocation, is common and linked with a favorable prognosis. However, the complete mutational profile contributing to leukemogenesis remains unclear. This study characterizes the mutational profile of the RUNX1-RUNX1T1 fusion in AML using Next-Generation Sequencing (NGS).Methods Twenty-four newly diagnosed AML patients were selected. DNA and RNA were extracted from bone marrow aspirate samples, and libraries were prepared using the Ion AmpliSeq™ Library Kit. Sequencing was performed on the Ion S5™ system, and data were analyzed using Torrent Suite™ and Ion Reporter™ Software. Variants were annotated, and their clinical significance was assessed via ClinVar. In silico prediction tools, including SIFT and PolyPhen-2, were used for functional impact assessment.Results Patients with RUNX1-RUNX1T1 fusion (n = 3) demonstrated higher initial peripheral blood and bone marrow blast counts and a pronounced prevalence of CD56 and CD19 positivity. The average number of mutations in KIT and NF1 was higher in the fusion group (p = 0.021 and p = 0.049, respectively). In total, 228 genetic variants were identified, with most associated with transcription/kinase signaling pathways (36.8%). Epigenetic regulators were the next most common category (21.5%). ClinVar data revealed pathogenic variants predominantly in the KIT gene, including two missense mutations, p.Asp816Val and p.Asp816Ala, at exon 17. Unique variants were identified exclusively in RUNX1-RUNX1T1 patients, including eight non-reported variants. Among these, a TET2 variant (p.Pro1367Leu) was predicted to have deleterious effects based on in silico tools.Conclusion The molecular profiling of RUNX1-RUNX1T1 fusion offers crucial insights into AML’s genetic landscape. Identifying therapeutic targets and novel variants broadens our understanding of mutations, presenting new research opportunities and potential interventions. |
| format | Article |
| id | doaj-art-a8afefcf9d974e1a9ddc5d5ce50dca6b |
| institution | Kabale University |
| issn | 2090-5068 2090-5076 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Alexandria Journal of Medicine |
| spelling | doaj-art-a8afefcf9d974e1a9ddc5d5ce50dca6b2024-11-22T08:38:06ZengTaylor & Francis GroupAlexandria Journal of Medicine2090-50682090-50762024-12-0160128228910.1080/20905068.2024.2387881Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusionMagdy Elbordiny0Reham AboElwafa1Abeer Elhadidi2Ashraf Elghandour3Salma Elmasry4Department of Clinical Pathology, Faculty of Medicine, Alexandria University, Alex, EGYPTDepartment of Clinical Pathology, Faculty of Medicine, Alexandria University, Alex, EGYPTDepartment of Clinical Pathology, Faculty of Medicine, Alexandria University, Alex, EGYPTHaematology Unit, Internal Medicine Department, Faculty of Medicine, Alexandria University, Alex, EGYPTDepartment of Clinical Pathology, Faculty of Medicine, Alexandria University, Alex, EGYPTIntroduction Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of immature myeloid cells. Among the genetic alterations in AML, the RUNX1- RUNX1T1 fusion, resulting from the t (8; 21) (q22; q22.1) translocation, is common and linked with a favorable prognosis. However, the complete mutational profile contributing to leukemogenesis remains unclear. This study characterizes the mutational profile of the RUNX1-RUNX1T1 fusion in AML using Next-Generation Sequencing (NGS).Methods Twenty-four newly diagnosed AML patients were selected. DNA and RNA were extracted from bone marrow aspirate samples, and libraries were prepared using the Ion AmpliSeq™ Library Kit. Sequencing was performed on the Ion S5™ system, and data were analyzed using Torrent Suite™ and Ion Reporter™ Software. Variants were annotated, and their clinical significance was assessed via ClinVar. In silico prediction tools, including SIFT and PolyPhen-2, were used for functional impact assessment.Results Patients with RUNX1-RUNX1T1 fusion (n = 3) demonstrated higher initial peripheral blood and bone marrow blast counts and a pronounced prevalence of CD56 and CD19 positivity. The average number of mutations in KIT and NF1 was higher in the fusion group (p = 0.021 and p = 0.049, respectively). In total, 228 genetic variants were identified, with most associated with transcription/kinase signaling pathways (36.8%). Epigenetic regulators were the next most common category (21.5%). ClinVar data revealed pathogenic variants predominantly in the KIT gene, including two missense mutations, p.Asp816Val and p.Asp816Ala, at exon 17. Unique variants were identified exclusively in RUNX1-RUNX1T1 patients, including eight non-reported variants. Among these, a TET2 variant (p.Pro1367Leu) was predicted to have deleterious effects based on in silico tools.Conclusion The molecular profiling of RUNX1-RUNX1T1 fusion offers crucial insights into AML’s genetic landscape. Identifying therapeutic targets and novel variants broadens our understanding of mutations, presenting new research opportunities and potential interventions.https://www.tandfonline.com/doi/10.1080/20905068.2024.2387881Acute myeloid leukemia (AML)Next-Generation Sequencing (NGS)RUNX1-RUNX1T1 fusion |
| spellingShingle | Magdy Elbordiny Reham AboElwafa Abeer Elhadidi Ashraf Elghandour Salma Elmasry Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion Alexandria Journal of Medicine Acute myeloid leukemia (AML) Next-Generation Sequencing (NGS) RUNX1-RUNX1T1 fusion |
| title | Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion |
| title_full | Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion |
| title_fullStr | Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion |
| title_full_unstemmed | Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion |
| title_short | Molecular profiling of acute myeloid leukemia with Runx1-Runx1t1 fusion |
| title_sort | molecular profiling of acute myeloid leukemia with runx1 runx1t1 fusion |
| topic | Acute myeloid leukemia (AML) Next-Generation Sequencing (NGS) RUNX1-RUNX1T1 fusion |
| url | https://www.tandfonline.com/doi/10.1080/20905068.2024.2387881 |
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