泰国东北部急性髓性白血病患者FLT3基因突变

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2022-11-24 DOI:10.12659/MSMBR.937446
Nang Ei Ei Aung, Supawadee Yamsri, Nattiya Teawtrakul, Piyawan Kamsaen, Supan Fucharoen
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引用次数: 7

摘要

FLT3基因突变与急性髓性白血病(AML)有关。在大约30%的新发AML患者中发现FLT3突变,特别是那些具有典型核型和预后较差的患者。因此,我们研究了泰国东北部AML患者FLT3基因内部串联重复(ITD)和错义突变的频率及其相关临床特征。材料和方法本研究纳入了2020年1月至2021年5月期间从泰国东北部Khon Kaen大学Srinagarind医院招募的65名新诊断的AML患者的剩余骨髓和/或外周血标本。利用pcr相关技术扩增FLT3- itd和FLT3-酪氨酸激酶结构域(TKD)。结果FLT3-ITD和TKD的发生率分别为16.9%(11/65)和10.8%(7/65)。一名患者有ITD和TKD突变。flt3 - itd阳性患者的白细胞计数和外周细胞百分率均显著高于flt3 -野生型患者,而flt3 - tkd阳性患者的外周细胞百分率显著低于flt3 -野生型患者。flt3阳性和flt3野生型患者无其他临床特征。DNA测序鉴定出4个FLT3-TKD突变。的c.2504A > T;Asp835Val和C . 2503g >C;Asp835His突变预测为致病性突变,而2个新突变c.2508C>A;Ile836= and c.2508C>G;预测Ile836Met为中性突变。该研究首次表明,FLT3-TKD突变在泰国东北部AML患者中很常见。这些数据对于为患者选择有效的靶向治疗方案是有用的。
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FLT3 Gene Mutations in Acute Myeloid Leukemia Patients in Northeast Thailand.

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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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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