Department of Clinical Pathology, Faculty of Medicine, Tanta University, Tanta, Egypt.
Department of Laboratory Medicine, Faculty of Applied Medical Science, Umm Al-Qura University, Makkah, KSA.
Cell Mol Biol (Noisy-le-grand). 2021 Nov 25;67(3):92-98. doi: 10.14715/cmb/2021.67.3.12.
Despite the great advance in treatment, cytogenetically normal Acute myeloid leukemia (CN-AML) is still a challenging entity. The discovery of IDH1 mutation in AML together with the frequent co-mutations; NPM1 and FLT3-ITD throughs a new insight into the pathogenesis and outcome of CN-AML. Recently, there has been an increasing number of recurring mutations in other genes for which the forecasting effect is still required. Despite the large number of risk variables established, there are relatively few prognostic indicators that can help in treatment decisions in AML patients. This study aimed at recording the frequency of IDH1 and NPM1 mutations in newly diagnosed AML and, dual clinicopathological significance. IDH1 and NPM1 mutations were analyzed using High-Resolution Melting curve analysis PCR in 78 newly diagnosed AML patients; 30 pediatric and 48 adult AML patients. IDH1 mutation was detected in 6 out of the 48 adult AML cases (12.5%) and all of them had intermediate cytogenetic prognostic stratification. 5/6 mutant IDH1 patients showed NPM1 co-mutation (P-value= 0.008). Mutant IDH1 patients showed significant resistance to induction therapy (P-value <0.001) and even those who achieved complete remission were relapsed later. Within the intermediate cytogenetic group, the IDH1 mutated patients had short overall survival (HR 12.9, 95% CI (3.1- 53.45) and event-free survival (HR 15.7, 95% CI (2.99-82.72) and P-value <0.001). IDH1 mutation is closely linked to the intermediate cytogenetic stratified group and in particular old age patients and has a great impact on their survival.
尽管治疗取得了重大进展，但细胞遗传学正常的急性髓系白血病（CN-AML）仍然是一个具有挑战性的实体。AML 中 IDH1 突变的发现以及 NPM1 和 FLT3-ITD 的频繁共突变，为 CN-AML 的发病机制和预后提供了新的认识。最近，越来越多的其他基因经常出现复发突变，这些突变仍需要预测效果。尽管已经确定了大量的风险变量，但在 AML 患者的治疗决策中，能够提供预后信息的指标相对较少。本研究旨在记录新诊断的 AML 中 IDH1 和 NPM1 突变的频率，并分析其双重临床病理意义。我们使用高分辨率熔解曲线分析 PCR 对 78 例新诊断的 AML 患者（30 例儿科和 48 例成人 AML 患者）进行 IDH1 和 NPM1 突变分析。在 48 例成人 AML 病例中，有 6 例检测到 IDH1 突变（12.5%），所有患者均具有中等细胞遗传学预后分层。5/6 例突变 IDH1 患者显示 NPM1 共突变（P 值=0.008）。突变 IDH1 患者对诱导治疗有明显的耐药性（P 值<0.001），甚至那些达到完全缓解的患者也会随后复发。在中等细胞遗传学组中，IDH1 突变患者的总生存时间（HR 12.9，95%CI（3.1-53.45）和无事件生存时间（HR 15.7，95%CI（2.99-82.72）较短，P 值均<0.001）。IDH1 突变与中等细胞遗传学分层组密切相关，特别是与老年患者密切相关，对其生存有重大影响。
