急性髓系白血病患者 FLT3、NPM1、DNMT3A 和 TP53 突变的分子和临床意义。
Molecular and clinical significance of FLT3, NPM1, DNMT3A and TP53 mutations in acute myeloid leukemia patients.
发表日期:2023 Aug 04
作者:
Ayad M Ali, Gaza F Salih
来源:
Cellular & Molecular Immunology
摘要:
急性髓性白血病(AML)是一种影响骨髓和血细胞的血液癌症。AML的特征是异常白细胞,即髓母细胞的快速生长和积累,这些细胞干扰了正常血细胞的生成。主要目的是确定这些遗传变异与AML伊拉克患者的临床血液学参数、预后因素和治疗的关系。我们使用Sanger测序方法检测了76例AML患者的突变。回顾性分析AML患者的临床数据以比较每个基因突变组的预后情况。在核心致病基因组中,约47.4%的纳入患者发现了体细胞突变,包括FLT3(18例,23.7%),DNMT3A(14例,18.4%),NPM1(11例,14.5%)和TP53(5例,6.8%)。由于多个突变常常同时存在于同一患者中,我们将患者分为另外10个组。两个新的FLT3-ITD突变在NCBI GenBank中提交了新的访问号码(OP807465和OP807466)。这两个新的突变经过计算分析后被预测为致病突变。我们发现在急性治疗后(缓解、失败和死亡)疾病进展方面,患者有或没有检测到的突变之间存在显着差异(pv<0.001),并且在总白细胞计数方面存在显着统计差异(pv<0.0001)。这些基因是AML患者中最常见的突变基因之一。了解这些突变的分子和临床意义对指导治疗决策和预测患者预后至关重要。© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Acute myeloid leukemia (AML) is a type of blood cancer that affects the bone marrow and blood cells. AML is characterized by the rapid growth and accumulation of abnormal white blood cells, known as myeloblasts, which interfere with the production of normal blood cells.The main aim was to determine the relationship between these genetic alterations and the clinico-haematological parameters and prognostic factors with therapy for Iraqi patients with AML.We used Sanger Sequencing to detect the mutations in 76 AML patients. Clinical data of AML patients were retrospectively analysed to compare the prognosis of each gene mutation group.Somatic mutations were identified in 47.4% of the enrolled patients in a core set of pathogenic genes, including FLT3 (18 patients, 23.7%), DNMT3A (14, 18.4%), NPM1 (11, 14.5%) and TP53 (5, 6.8%). As multiple mutations frequently coexisted in the same patient, we classified patients into 10 further groups. Two novel mutations were detected in FLT3-ITD, with new accession numbers deposited into NCBI GenBank (OP807465 and OP807466). These two novel mutations were computationally analysed and predicted as disease-causing mutations. We found significant differences between patients with and without the detected mutations in disease progression after induction therapy (remission, failure and death; pv = < 0.001) and statistically significant differences were reported in total leukocyte count (pv = < 0.0001).These genes are among the most frequently mutated genes in AML patients. Understanding the molecular and clinical significance of these mutations is important for guiding treatment decisions and predicting patient outcomes.© 2023. The Author(s), under exclusive licence to Springer Nature B.V.