Panel-based next-generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings
Panel-based next-generation sequencing facilitates the characterization of childhood acute myeloid leukemia in clinical settings
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DOI：
10.3892/br.2020.1353
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发表时间：
2020-11-01
影响因子：
2.3
通讯作者：
Shimada, Akira
中科院分区：
文献类型：
--
作者：
Ishida, Hisashi;Iguchi, Akihiro;Shimada, Akira
急性髓系白血病(AML)约占儿童白血病病例的20%。近几十年来，儿童AML的预后有所改善，但它落后于大多数其他类型的儿童癌症，死亡率为30%-40%。因此，需要更新的、更有针对性的药物才能纳入治疗计划。这些较新的药物选择性地针对具有特定基因改变的AML细胞。然而，成人AML患者和儿童AML患者之间的基因改变存在显著差异。在本研究中，对27例AML儿童患者的诊断、缓解和复发(如果有的话)样本进行了廉价和快速的下一代测序(NGS；150个癌症相关基因)。在这项分析中，有7个基因发生了反复突变。KRAS突变7例，NRAS突变3例，KIT、GATA1、WT1、PTPN11、JAK3和Flt3各突变2例。在复发的AML患者中，有6名患者在确诊时携带KRAS突变；然而，其中4名患者在复发时丢失了这些突变。此外，在最终复发的患者中发现了两种基因变化(Flt3-ITD和TP53变化)，据报道，这些突变是成人AML患者的不利预后因素。这种基于小组的靶向测序方法可能有助于确定儿童AML的遗传背景，并改善对治疗反应的预测和对潜在靶向基因改变的检测。RAS通路突变在复发时高度不稳定；因此，应谨慎选择这些突变作为靶点。将这种基于小组的NGS方法结合到临床环境中，可能会允许以患者为导向的儿童AML精确治疗策略。
Acute myeloid leukemia (AML) accounts for similar to 20% of pediatric leukemia cases. The prognosis of pediatric AML has been improved in recent decades, but it trails that of most other types of pediatric cancer, with mortality rates of 30-40%. Consequently, newer more targeted drugs are required for incorporation into treatment plans. These newer drugs selectively target AML cells with specific gene alterations. However, there are significant differences in genetic alterations between adult and pediatric patients with AML. In the present study, inexpensive and rapid next-generation sequencing (NGS) of >150 cancer-related genes was performed for matched diagnostic, remission and relapse (if any) samples from 27 pediatric patients with AML. In this analysis, seven genes were recurrently mutated. KRAS was mutated in seven patients, NRAS was mutated in three patients, and KIT, GATA1, WT1, PTPN11, JAK3 and FLT3 were each mutated in two patients. Among patients with relapsed AML, six harbored KRAS mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (FLT3-ITD and TP53 alterations) were detected among patients who eventually relapsed, and these mutations are reported to be adverse prognostic factors for adult patients with AML. This panel-based, targeted sequencing approach may be useful in determining the genetic background of pediatric AML and improving the prediction of treatment response and detection of potentially targetable gene alterations. RAS pathway mutations were highly unstable at relapse; therefore, these mutations should be chosen as a target with caution. Incorporating this panel-based NGS approach into the clinical setting may allow for a patient-oriented strategy of precision treatment for childhood AML.