Yu Jifeng, Li Yingmei, Li Tao, Li Yafei, Xing Haizhou, Sun Hui, Sun Ling, Wan Dingming, Liu Yanfang, Xie Xinsheng, Jiang Zhongxing
Department of Hematology, The First Affiliated Hospital of Zhengzhou University, 1 East Jianshe Road, Zhengzhou, 450052 China.
Exp Hematol Oncol. 2020 Jan 6;9:2. doi: 10.1186/s40164-019-0158-5. eCollection 2020.
In this study, we retrospectively summarized the differences of molecular gene mutations between MDS and AML patients, as well as the young and older age groups of MDS and AML patients. We also analyzed the response of newly diagnosed AML patients to standard DA or IA induction chemotherapy and the relationship between the chemotherapy outcome and the frequency of different gene mutation abnormalities.
NGS assay covering 43 genes was studied in 93 de novo MDS and 325 non-M3 AML patients. Bone marrow samples from all patients underwent gene mutational analysis by NGS.
At least one non-synonymous gene mutation was detected in 279 AML patients (85.8%) and 85 MDS patients (91.4%). Contrary to 59 years and younger AML patients, there was a significantly higher incidence of gene mutation in 60 years and older AML patients (2.37 vs 1.94, p = 0.034). Gene mutation incidence in 60 years and older MDS patients increased, but no statistical significance was present (1.95 vs 1.64, p = 0.216). AML patients had a significantly higher gene mutation incidence compared with MDS-MLD patients (2.02 vs 1.63, p = 0.046). Gene mutation incidence was higher in patients with MDS-EB1/EB2 compared with patients with MDS-MLD but there was no statistical significance present (2.14 vs 1.63, p = 0.081). AML patients had significantly higher incidences of CEBPA, FLT3-ITD, DNMT3A, NPM1 and IDH1/2 gene mutations (p = 0.0043, 0.000, 0.030962, 0.002752, and 0.000628, respectively) and a lower incidence of TET2 and U2AF1 gene mutations (p = 0.000004 and 0.000, respectively) compared with MDS patients. Among the individual genes in different age groups, there were significantly higher incidences of RUNX1, IDH2, TP53 and SF3B1 gene mutations (p = 0.0478, 0.0028, 0.0024 and 0.005, respectively) as well as a trend of higher ASXL gene mutation (p = 0.057) in 60 years and older AML patients compared to 59 years and younger patients. There was no statistically significant difference in MDS patients with the different age groups and among the individual genes. Between AML patients and MDS patients among the different gene functional groups, AML patients had a significantly higher incidence of transcriptional deregulation (27.4% vs 15.1%, p = 0.014963), activated signalling (36.3% vs 10.8%, p = 0.000002) related gene mutations as well as a significantly lower incidence of RNA spliceosome (6.15% vs 60.1%, p = 0.000) related gene mutations. Furthermore, among the patients who received either IA or DA regimen for induction chemotherapy, patients with IA regimen had a significantly better CR rate than those with DA regimen (76.6% vs 57.1%, p = 0.0228).
Different gene mutations had been found in majority of MDS and AML patients. MDS and AML patients had different gene mutation patterns. AML patients with fewer or no gene mutations had a better chance of achieving CR when treated with IA and DA regimen induction chemotherapy.
在本研究中，我们回顾性总结了骨髓增生异常综合征（MDS）和急性髓系白血病（AML）患者之间以及MDS和AML患者的青年和老年组之间分子基因突变的差异。我们还分析了新诊断的AML患者对标准DA或IA诱导化疗的反应以及化疗结果与不同基因突变异常频率之间的关系。
对93例初发MDS患者和325例非M3 AML患者进行了覆盖43个基因的二代测序（NGS）检测。所有患者的骨髓样本均通过NGS进行基因突变分析。
在279例AML患者（85.8%）和85例MDS患者（91.4%）中检测到至少一种非同义基因突变。与59岁及以下的AML患者相反，60岁及以上的AML患者基因突变发生率显著更高（2.37对1.94，p = 0.034）。60岁及以上MDS患者的基因突变发生率有所增加，但无统计学意义（1.95对1.64，p = 0.216）。AML患者的基因突变发生率显著高于MDS-MLD患者（2.02对1.63，p = 0.046）。MDS-EB1/EB2患者的基因突变发生率高于MDS-MLD患者，但无统计学意义（2.14对1.63，p = 0.081）。与MDS患者相比，AML患者的CEBPA、FLT3-ITD、DNMT3A、NPM1和IDH1/2基因突变发生率显著更高（分别为p = 0.0043、0.000、0.030962、0.002752和0.000628），而TET2和U2AF1基因突变发生率较低（分别为p = 0.000004和0.000）。在不同年龄组的单个基因中，60岁及以上的AML患者与59岁及以下的患者相比，RUNX1、IDH2、TP53和SF3B1基因突变发生率显著更高（分别为p = 0.0478、0.0028、0.0024和0.005），ASXL基因突变也有升高趋势（p = 0.057）。MDS患者不同年龄组和单个基因之间无统计学显著差异。在不同基因功能组的AML患者和MDS患者之间，AML患者转录失调相关基因突变发生率显著更高（27.4%对15.1%，p = 0.014963）、激活信号相关基因突变发生率显著更高（36.3%对10.8%，p = 0.000002），而RNA剪接体相关基因突变发生率显著更低（6.15%对60.1%，p = 0.000）。此外，在接受IA或DA方案诱导化疗的患者中，接受IA方案的患者完全缓解（CR）率显著高于接受DA方案的患者（76.6%对57.1%，p = 0.0228）。
大多数MDS和AML患者存在不同的基因突变。MDS和AML患者有不同的基因突变模式。基因突变较少或无基因突变的AML患者在接受IA和DA方案诱导化疗时达到CR的机会更大。
