Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Division of Hematology and Medical Oncology, Department of Internal Medicine, Cipto Mangunkusumo National General Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Mol Biol Rep. 2024 Jul 29;51(1):867. doi: 10.1007/s11033-024-09790-1.
FLT3 gene mutations are genetic abnormality that caused leukemogenesis. Furthermore, presence of FLT3 mutations is associated with poor prognosis in AML. This study aimed to identify FLT3 gene mutations so that it can be used as a genetic reference for the AML patients in Indonesian population.
This cross-sectional study recruited 63 AML de novo patients between August 2021 and July 2023 at Cipto Mangukusumo General Hospital and Dharmais Cancer Hospital. We collected peripheral blood from the patients for DNA isolation. FLT3 gene mutation was detected using PCR method, then followed by the Sanger sequencing. Novel mutation in exon-14 continued to in silico study using SWISS MODEL server for modelling protein and PyMOL2 software for visualizing the protein model.
Frequency FLT3-ITD mutation was 22% and 6 (10%) patients had a novel mutation on juxtamembrane domain. The number of FLT3-ITD insertions was 24 bp to 111 bp, with a median of 72 bp. Novel mutation indicated a change in the protein sequence at amino acid number 572 from Tyrosine to Valine and formed a stop codon (UGA) at amino acid position ins572G573. In-silico study from novel mutation showed the receptor FLT3 protein was a loss of most of the juxtamembrane domain and the entire kinase domain.
A novel FLT3 gene mutation was found in this study in the juxtamembrane domain. Based on the sequencing analysis and in silico studies, this mutation is likely to affect the activity of the FLT3 receptor. Therefore, further studies on this novel mutation are needed.
FLT3 基因突变是导致白血病发生的遗传异常。此外，FLT3 突变的存在与 AML 患者的预后不良相关。本研究旨在鉴定 FLT3 基因突变，以便为印度尼西亚人群中的 AML 患者提供遗传参考。
本横断面研究于 2021 年 8 月至 2023 年 7 月期间在 Cipto Mangunkusumo 综合医院和 Dharmais 癌症医院招募了 63 例初发 AML 患者。我们从患者采集外周血用于 DNA 分离。使用 PCR 方法检测 FLT3 基因突变，然后进行 Sanger 测序。对外显子 14 中的新突变，我们继续使用 SWISS MODEL 服务器进行蛋白质建模的计算机研究，并使用 PyMOL2 软件进行蛋白质模型的可视化。
FLT3-ITD 突变的频率为 22%，有 6（10%）例患者在跨膜区有新的突变。FLT3-ITD 插入的数量为 24bp 至 111bp，中位数为 72bp。新突变导致氨基酸 572 处的酪氨酸变为缬氨酸，并且在氨基酸位置 ins572G573 形成一个终止密码子（UGA）。新突变的计算机研究表明，受体 FLT3 蛋白丢失了大部分跨膜区和整个激酶结构域。
本研究在跨膜区发现了一种新的 FLT3 基因突变。根据测序分析和计算机研究，该突变可能影响 FLT3 受体的活性。因此，需要对该新突变进行进一步的研究。
