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Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
FLT3 Gene Mutations in Acute Myeloid Leukemia Patients in Northeast Thailand
Nang Ei Ei Aung1, Supawadee Yamsri2, Nattiya Teawtrakul3
1Medical Science Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
Abstract:
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.
Insights
FLT3 mutations, common in acute myeloid leukemia (AML), were studied in northeast Thailand. FLT3-ITD and FLT3-TKD mutations were found in 16.9% and 10.8% of AML patients, respectively.
Area of Science:
- Hematology
- Molecular Biology
- Genetics
Background:
- Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene are prevalent in acute myeloid leukemia (AML), affecting prognosis.
- FLT3 mutations, including internal tandem duplications (ITD) and tyrosine kinase domain (TKD) missense mutations, are found in about 30% of de novo AML cases.
- Understanding the frequency and clinical impact of FLT3 mutations is crucial for developing targeted therapies in AML.
Purpose of the Study:
- To determine the frequencies of FLT3-ITD and FLT3-TKD mutations in AML patients from northeast Thailand.
- To investigate the association between FLT3 mutations and clinical characteristics in this patient cohort.
- To identify specific FLT3-TKD mutations and assess their potential pathogenicity.
Main Methods:
- Bone marrow and/or peripheral blood samples from 65 newly diagnosed AML patients were analyzed.
- Polymerase chain reaction (PCR) techniques were used to amplify FLT3-ITD and FLT3-TKD regions.
- DNA sequencing was performed to identify specific mutations and predict their pathogenicity.
Main Results:
- FLT3-ITD mutations were detected in 16.9% (11/65) and FLT3-TKD mutations in 10.8% (7/65) of patients.
- FLT3-ITD-positive patients showed significantly higher white blood cell counts and peripheral blast percentages compared to FLT3-wild-type patients.
- FLT3-TKD-positive patients had a significantly lower peripheral blast percentage; four distinct FLT3-TKD mutations were identified, with two predicted as pathogenic and two as neutral.
Conclusions:
- This study reveals a significant prevalence of FLT3-TKD mutations among AML patients in northeast Thailand.
- FLT3-ITD and FLT3-TKD mutations are associated with distinct clinical features in AML patients.
- The findings provide valuable insights for tailoring targeted treatment strategies for AML patients in this region.

