Department of Chemistry, College of Science, University of Garmian, Kalar, Iraq.
Department of Biology, College of Science, University of Sulaimani, Sulaymaniyah, Iraq.
Mol Biol Rep. 2023 Oct;50(10):8035-8048. doi: 10.1007/s11033-023-08680-2. Epub 2023 Aug 4.
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.
急性髓系白血病（AML）是一种影响骨髓和血细胞的血液系统癌症。AML 的特征是异常白细胞（称为原始细胞）的快速生长和积累，这些细胞干扰正常血细胞的产生。
主要目的是确定这些遗传改变与伊拉克 AML 患者的临床血液学参数和预后因素与治疗之间的关系。
我们使用 Sanger 测序检测了 76 名 AML 患者的突变。回顾性分析 AML 患者的临床数据，比较每个基因突变组的预后。
在一组核心致病基因中，47.4%的入组患者存在体细胞突变，包括 FLT3（18 例，23.7%）、DNMT3A（14 例，18.4%）、NPM1（11 例，14.5%）和 TP53（5 例，6.8%）。由于同一患者中经常存在多种突变，我们将患者进一步分为 10 组。在 FLT3-ITD 中检测到两个新的突变，新的登录号已存入 NCBI GenBank（OP807465 和 OP807466）。这两个新突变通过计算分析并预测为致病变异。我们发现诱导治疗后疾病进展（缓解、失败和死亡）患者中存在有或不存在检测到的突变之间存在显著差异（pv = < 0.001），总白细胞计数也存在统计学差异（pv = < 0.0001）。
这些基因是 AML 患者中最常突变的基因之一。了解这些突变的分子和临床意义对于指导治疗决策和预测患者预后非常重要。
