The detection of internal tandem duplication in the FMS-like tyrosine kinase 3 gene in a sample of Iraqi patients with acute myeloid leukemia
DOI:
https://doi.org/10.15584/ejcem.2025.3.6Keywords:
acute myeloid leukemia, capillary electrophoresis, FAB, FLT3-ITD mutation, sex disparityAbstract
Introduction and aim. Acute myeloid leukemia (AML) is a genetically heterogeneous malignancy significantly influenced by FMS-like tyrosine kinase 3 mutations. This study investigated the prevalence and clinical implications of internal tandem duplication (ITD) mutations in FLT3 in patients with AML in Iraq.
Material and methods. The study involved blood samples collected from 50 newly diagnosed AML and 50 healthy subjects between April 2023 and January 2024 and used for conventional PCR. PCR products positive for the ITD mutation were subjected to fragment analysis using capillary electrophoresis (CF) to confirm ITD mutations.
Results. FLT3-ITD mutations were identified in 20% of patients with AML (10/50), with striking female predominance (90% of mutation-positive cases). Based on the FAB classification, M5 was the most prevalent FAB subtype among mutation carriers (40%), with no mutations detected in M7.
Conclusion. This study provides critical information on the prevalence and clinical implications of FLT3-ITD mutations in patients with AML in Iraqi, emphasizing the need for precise molecular diagnostic approaches. This finding revealed a distinct subset of patients with AML that harbor FLT3-ITD mutations, with a significant proportion exhibiting elevated allelic ratios, which reinforces their prognostic relevance.
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Perzolli A, Koedijk JB, Zwaan CM, Heidenreich O. Targeting the innate immune system in pediatric and adult AML. Leukemia. 2024;38(6):1191-1201. doi: 10.1038/s41375-024-02217-7.
Lafta M, AL-Amili WA, Alwan AF, Khalaf IAH. Relationship between the drug responsiveness of acute myeloid leukemia Iraqi patients and gene expression of drug resistance ABCB1 and ABCG2 genes. Iraqi J Biotechnol. 2022;21(1):1-7. doi: index.php/IJB/article/view/445/334
Dawood HH, Mohammed RK. The Association between Single Nucleotide Polymorphisms rs1042522 and rs1642785 in the TP53 gene and Acute Myeloid leukemia in a sample of the Baghdad/Iraq population. Baghdad Sci J. 2024;21(3):0909-0918. doi: 10.21123/bsj.2023.8207
Dawood HH, Mohammed RK. The Correlation Study between TP53 Gene Expression and Acute Myeloid Leukemia in Iraq. Iraqi J Sci. 2023; 64(11):5615-5623. doi: 10.24996/ijs.2023.64.11.14
Mohammed SK, AL-Faisal AHM. Study of Chromosomal Aberrations and Micronucleus Formation in Some Iraqi Patients infected with Acute Myeloid Leukemia (AML). Iraqi J Biotechnol. 2014;13(1):68-77.
Board IC. Annual Report of Iraqi Cancer Registry. Iraq Cancer Regist. 2020;(01):1-10.
Mohammed SK, Al-faisal AHM. A Study of FLT/ITD Mutations in Cytogenetically Normal Iraqi Acute Myeloid Leukemia Patients. Iraqi J Biotechnol. 2014;13(2): 152-160.
Li EW, Tran NYK, McCulloch D, et al. FLT3-TKD Measurable Residual Disease Detection Using Droplet Digital PCR and Clinical Applications in Acute Myeloid Leukemia. Int J Mol Sci. 2024;25(11):5771. doi: 10.3390/ijms25115771
Wang ES, Goldberg AD, Tallman M, et al. Crenolanib and intensive chemotherapy in adults with newly diagnosed FLT3-mutated AML. J Clin Oncol. 2024;42(15):1776-1787. doi: 10.1200/JCO.23.01061
Ruglioni M, Crucitta S, Luculli GI, et al. Understanding mechanisms of resistance to FLT3 inhibitors in adult FLT3-mutated Acute Myeloid Leukemia (AML) to guide treatment strategy. Crit Rev Oncol Hematol. 2024:104424. doi: 10.1016/j.critrevonc.2024.104424
Reikvam H. Revisiting the prognostic role of FLT3 mutations in acute myelogenous leukemia. Expert Rev Hematol. 2023;16(5):317-323. doi: 10.1080/17474086.2023.2202849
Jentzsch M, Bischof L, Brauer D, et al. Clinical implications of the FLT3-ITD allelic ratio in acute myeloid leukemia in the context of an allogeneic stem cell transplantation. Cancers (Basel). 2023;15(4):1312. doi: 10.3390/cancers15041312
Al-Mawali A, Gillis D, Lewis I. Characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplication in the FLT3 gene. Oman Med J. 2013;28(6):432. doi: 10.5001/omj.2013.121
Lagunas-Rangel FA, Chávez-Valencia V. FLT3–ITD and its current role in acute myeloid leukaemia. Med Oncol. 2017;34:1-13. doi: 10.1007/s12032-017-0970-x
Kennedy VE, Smith CC. FLT3 mutations in acute myeloid leukemia: key concepts and emerging controversies. Front Oncol. 2020;10:612880. doi: 10.3389/fonc.2020.612880
Latif NJ, Al-Rubaie HA. Impact of Plasma Focal Adhesion Kinase, Ephrin Receptor Type A4, and Adiponectin in Patients with Acute Myeloid Leukemia. J Appl Hematol. 2024;15(3):233-239. doi: 10.4103/joah.joah_37_24
Al-Shammari HHJ, Al-Rubaie HA, Al-Badran IM. Molecular Alterations in IDH 1/2 Genes among Iraqi Adult Acute Myeloid Leukemia Patients: Their Response to Treatment. J Appl Hematol. 2023;14(2):87-94. doi: 10.4103/joah.joah_79_22
Thiede C, Steudel C, Mohr B, et al. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis: Presented in part at the 42nd Annual Meeting of the American Society of Hematology, D. Blood, J Am Soc Hematol. 2002;99(12):4326-4335. doi: 10.1182/blood.V99.12.4326
Al-Husseinawi EKD, Subh S. Al-Mudallel, Maysaa A. Hematol Oncol. 2009;27:171-181.
Fahad LA, Al-Omar ZM, AL-Kheroo KN. Evaluation of FLT3-ITD Mutation in Fifty Newly Diagnosed Iraqi Patients with Acute Myeloid Leukemia. Ann Coll Med Mosul June. 2024;46(1):28-35. doi: 10.33899/mmed.2024.145893.1248
Hamed HR, AL-Jumaily RMK, Kadhom AE. Characterization of NPM1 and FLT3-ITD Mutations in Iraqi Patients with AML. Medico-legal Updat. 2021;21(2):133. doi: 10.37506/mlu.v21i2.2659
Dhahir EK, Al-Mudallel SS, Dhahi MAR. The Frequency of FLT3 Mutation in Fifty Five Iraqi Adult Patients with Acute Myeloid Leukemia. Iraqi J Med Sci. 2012;10(2):140-147.
Daver N, Schlenk RF, Russell NH, Levis MJ. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia. 2019;33(2):299-312. doi: s41375-018-0357-9
Sakaguchi M, Nakajima N, Yamaguchi H, et al. The sensitivity of the FLT3-ITD detection method is an important consideration when diagnosing acute myeloid leukemia. Leuk Res reports. 2020;13:100198. doi: 10.1016/j.Lrr.2020.100198
Travaglini S, Angelini DF, Alfonso V, et al. Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells. Blood Cancer J. 2020;10(8):85. doi: s41408-020-00352-9
Lee BH, Tothova Z, Levine RL, et al. FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia. Cancer Cell. 2007;12(4):367-380. doi: S1535-6108(07)00263-2
Daver N, Wei AH, Pollyea DA, Fathi AT, Vyas P, DiNardo CD. New directions for emerging therapies in acute myeloid leukemia: the next chapter. Blood Cancer J. 2020;10(10):107. doi: s41408-020-00376-1
Jain H, Eipe T, Shetty A, et al. Real-World Analysis Evaluating Treatment Eligibility and Outcomes in Patients With AML Receiving Intensive Chemotherapy: Insights From an Underrepresented Population. JCO Glob Oncol. 2025;11:e2400482. doi: 10.1200/GO-24-00482
Carbonell D, Chicano M, Cardero AJ, et al. FLT3-ITD Expression as a Potential Biomarker for the Assessment of Treatment Response in Patients with Acute Myeloid Leukemia. Cancers (Basel). 2022;14(16):4006. doi: 10.3390/cancers14164006
Al-Husseinawi EK. A pilot study for the detection of FLT3-ITD mutation frequency in 25 Iraqi patients with acute lymphoid leukemia in 2 Iraqi hospitals. J Pediatr Hematol Oncol. 2014;36(4):e207-e211. doi: 10.1097/MPH.0000000000000091
Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood, J Am Soc Hematol. 2022;140(12):1345-1377. doi: 10.1182/blood.2022016867
Zhou C, Zheng F, Xu L, et al. FLT3-ITD Allelic Ratio and NPM1 Mutation Do Not Impact Outcomes in Acute Myeloid Leukemia Patients with FLT3-ITD after Allogeneic Hematopoietic Stem Cell Transplantation: A Retrospective Propensity Score-Matching Study. Transplant Cell Ther. 2023;29(7):456.e1-456.e11. doi: 10.1016/j.jtct.2023.03.033
Kivioja J, Malani D, Kumar A, et al. FLT3-ITD allelic ratio and HLF expression predict FLT3 inhibitor efficacy in adult AML. Sci Rep. 2021;11(1):23565. doi: s41598-021-03010-7
Sarojam S, Vijay S, Raveendran S, Sreedharan J, Narayanan G, Sreedharan H. FLT3 Mutation as a Significant Prognostic Marker in de novo Acute Myeloid Leukemia Patients: Incidence, Distribution and Association with Cytogenetic Findings in a Study from South India. Middle East J Cancer. 2014;5(4):185-196.
Hellesøy M, Engen C, Grob T, Löwenberg B, Valk PJM, Gjertsen BT. Sex disparity in acute myeloid leukaemia with FLT3 internal tandem duplication mutations: implications for prognosis. Mol Oncol. 2021;15(9):2285-2299. doi: 10.1002/1878-0261.13035
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