Sino-US Diagnostics Lab, Tianjin Enterprise Key Laboratory of AI-aided Hematopathology Diagnosis, Tianjin, China.
Department of Hematology, Wuxi People's Hospital, Nanjing Medical University, Wuxi, China.
Int J Lab Hematol. 2023 Jun;45(3):353-359. doi: 10.1111/ijlh.14034. Epub 2023 Feb 7.
Measurable residual disease (MRD) is a prognostic factor for acute myeloid leukemia (AML). A next-generation sequencing (NGS) based MRD panel was developed and the results were validated.
The NGS sequencing data was collected from 1003 Chinese AML patients.
The sequencing data from 586 newly diagnosed AML patients showed that NRAS mutation was most common (20.8%), followed by NPM1 (19.4%), FLT3-ITD (18.5%), and DNMT3A (15.4%). NPM1 and FLT3-ITD mutations were less in Chinese than in Caucasian AML patients, and the result of KRAS mutation was opposite. A new panel named "AML NGS-MRD hot-spot panel" was designed, containing 178 hot-spot exons from 52 mutated genes and only 62.8 Kb in size. With this hot-spot panel, 92.5% newly diagnosed AML patients were found to carry ≥1 mutations. To verify the performance of this panel, additional 205 newly diagnosed AML patients and 212 post-treatment AML patients were evaluated, and the hot-spot panel achieved a similar detection rate (91.2% for newly diagnosed AML patients and 89.2% for post-treatment AML patients). Finally, this study found that the mutation frequencies of signaling pathway genes (e.g., KRAS, NRAS, FLT3-ITD, KIT) were significantly reduced in post-treatment AML.
The "AML NGS-MRD hot-spot panel" detected the mutations from relapsed AML patients with minimal panel size, and was a reliable and cost-effective panel for AML patients.
微小残留病灶（MRD）是急性髓系白血病（AML）的预后因素。本研究开发了一种基于下一代测序（NGS）的 MRD 检测 panel，并对其检测结果进行了验证。
收集了 1003 例中国 AML 患者的 NGS 测序数据。
586 例初诊 AML 患者的测序数据显示，NRAS 突变最为常见（20.8%），其次是 NPM1（19.4%）、FLT3-ITD（18.5%）和 DNMT3A（15.4%）。与高加索 AML 患者相比，NPM1 和 FLT3-ITD 突变在中国 AML 患者中较少见，KRAS 突变的结果则相反。设计了一个名为“AML NGS-MRD 热点 panel”的新 panel，包含 52 个突变基因的 178 个热点外显子，大小仅为 62.8 Kb。使用该热点 panel，92.5%的初诊 AML 患者携带≥1 个突变。为了验证该 panel 的性能，还对另外 205 例初诊 AML 患者和 212 例治疗后 AML 患者进行了评估，热点 panel 的检测率相似（初诊 AML 患者为 91.2%，治疗后 AML 患者为 89.2%）。最后，本研究发现治疗后 AML 患者信号通路基因（如 KRAS、NRAS、FLT3-ITD、KIT）的突变频率显著降低。
“AML NGS-MRD 热点 panel”使用最小的 panel 大小检测复发 AML 患者的突变，是一种可靠且具有成本效益的 AML 患者检测 panel。
