FLT3 Gene Mutations in Acute Myeloid Leukemia Patients in Northeast Thailand

医学 髓系白血病 错义突变 突变 基因突变 白细胞 内科学 骨髓 基因 肿瘤科 遗传学 生物
作者
Nang Ei Ei Aung,Supawadee Yamsri,Nattiya Teawtrakul,Piyawan Kamsaen,Supan Fucharoen
出处
期刊:Medical science monitor basic research [International Scientific Information Inc.]
卷期号:28
标识
DOI:10.12659/msmbr.937446
摘要

BACKGROUND Mutations in the FLT3 gene are associated with acute myeloid leukemia (AML). FLT3 mutations have been identified in approximately 30% of de novo AML patients, particularly those with typical karyotype and inferior prognosis. Therefore, we examined the frequencies of an internal tandem duplication (ITD) and missense mutations of the FLT3 gene and their associated clinical characteristics in patients with AML in northeast Thailand. MATERIAL AND METHODS The leftover bone marrow and/or peripheral blood specimens of 65 newly diagnosed AML patients recruited from Srinagarind Hospital, Khon Kaen University, northeast Thailand, between January 2020 and May 2021 were included in this study. FLT3-ITD and FLT3- tyrosine kinase domain (TKD) were amplified using PCR-related techniques. RESULTS The frequencies of FLT3-ITD and TKD were found to be 16.9% (11/65) and 10.8% (7/65), respectively. One patient had ITD and TKD mutations. The white blood cell count and peripheral blast percentage of FLT3-ITD-positive patients were statistically significantly higher than those of the FLT3-wild type patients, while the peripheral blast percentage of FLT3-TKD-positive patients was significantly lower. No other clinical characteristics among FLT3-positive and FLT3-wild-type patients were observed. DNA sequencing identified 4 FLT3-TKD mutations. The c.2504A>T; Asp835Val and c.2503G>C; Asp835His mutations were predicted as pathogenic mutations while the 2 novel mutations, c.2508C>A; Ile836= and c.2508C>G; Ile836Met were predicted as neutral mutations. CONCLUSIONS This study showed for the first time that FLT3-TKD mutation is common among northeast Thai AML patients. The data should prove useful for selecting efficacious targeted treatment plans for the patients.
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