Ishida Hisashi, Iguchi Akihiro, Aoe Michinori, Nishiuchi Ritsuo, Matsubara Takehiro, Keino Dai, Sanada Masashi, Shimada Akira
Department of Pediatrics/Pediatric Hematology and Oncology, Okayama University Hospital, Okayama 700-8558, Japan.
Department of Pediatrics, Hokkaido University Hospital, Sapporo, Hokkaido 060-8648, Japan.
Biomed Rep. 2020 Nov;13(5):46. doi: 10.3892/br.2020.1353. Epub 2020 Aug 28.
Acute myeloid leukemia (AML) accounts for ~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. was mutated in seven patients, was mutated in three patients, and , , , , and were each mutated in two patients. Among patients with relapsed AML, six harbored mutations at diagnosis; however, four of these patients lost these mutations at relapse. Additionally, two genetic alterations (-ITD and 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.
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，但仍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、更具针对性的药物纳入治疗方案。这些新药选择性地靶向具有特定基因改变的AML细胞。然而，成年和儿童AML患者的基因改变存在显著差异。在本研究中，对27例儿童AML患者的配对诊断、缓解和复发（如有）样本进行了150多个癌症相关基因的低成本快速下一代测序（NGS）。在该分析中，有7个基因反复发生突变。7例患者发生 突变，3例患者发生 突变， 、 、 、 、 和 各有2例患者发生突变。在复发的AML患者中，6例在诊断时有 突变；然而，这些患者中有4例在复发时失去了这些突变。此外，在最终复发的患者中检测到两种基因改变（-ITD和 改变），据报道这些突变是成年AML患者的不良预后因素。这种基于基因panel的靶向测序方法可能有助于确定儿童AML的遗传背景，改善治疗反应预测以及检测潜在的可靶向基因改变。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。将这种基于基因panel的NGS方法纳入临床环境可能会为儿童AML提供以患者为导向的精准治疗策略。
