Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemia.
Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemia.
复制标题
DOI：
10.3343/alm.2023.43.4.328
复制
发表时间：
2023-07-01
影响因子：
4.9
通讯作者：
Cheong, June -Won
中科院分区：
文献类型：
--
作者：
Kim, Jin Ju;Jang, Ji Eun;Lee, Hyeon Ah;Park, Mi Ri;Kook, Hye Won;Lee, Seung-Tae;Choi, Jong Rak;Min, Yoo Hong;Shin, Saeam;Cheong, June -Won
AML是一种异质性疾病，尽管进行了强化治疗，但达到细胞形态学缓解标准（残留肿瘤负荷[可测量残留病灶，MRD]<5%）的AML患者复发率仍然很高。本研究旨在开发一种靶向下一代测序 (NGS) 组合来检测 AML 患者的 MRD 并验证其性能。我们设计了一个纠错的、有针对性的 MRD-NGS 面板，不使用物理分子条形码，包括 24 个基因。使用该面板对 23 名 AML 患者的 54 份骨髓和外周血样本进行了测序。使用参考材料验证面板设计，并使用液滴数字 PCR 评估准确性。稀释测试显示出良好的线性度以及预期和观察到的克隆频率之间的强相关性 (R>0.99)。该测试可重复检测三个稀释系列样品中的 MRD，对单核苷酸变异的灵敏度为 0.25%。化疗一个月后形态缓解的患者样本中超过一半具有可检测到的突变。化疗一个月后收集的样本的 NGS-MRD 阳性往往与较差的总生存期和无进展生存期相关。我们高度灵敏且准确的 NGS-MRD 组合可轻松用于监测临床实践中的大多数 AML 患者，包括没有基因重排的患者。此外，该 NGS-MRD 组合可能允许在临床复发期间检测新出现的克隆，从而实现更可靠的 AML 预后。
AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]<5%). This study aimed to develop a targeted next-generation sequencing (NGS) panel to detect MRD in AML patients and validate its performance. We designed an error-corrected, targeted MRD-NGS panel without using physical molecular barcodes, including 24 genes. Fifty-four bone marrow and peripheral blood samples from 23 AML patients were sequenced using the panel. The panel design was validated using reference material, and accuracy was assessed using droplet digital PCR. Dilution tests showed excellent linearity and a strong correlation between expected and observed clonal frequencies (R>0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival. Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.
登录
查看更多内容
影响因子：
82.9
作者：
Li S;Garrett-Bakelman FE;Chung SS;Sanders MA;Hricik T;Rapaport F;Patel J;Dillon R;Vijay P;Brown AL;Perl AE;Cannon J;Bullinger L;Luger S;Becker M;Lewis ID;To LB;Delwel R;Löwenberg B;Döhner H;Döhner K;Guzman ML;Hassane DC;Roboz GJ;Grimwade D;Valk PJ;D'Andrea RJ;Carroll M;Park CY;Neuberg D;Levine R;Melnick AM;Mason CE
通讯作者：
Mason CE
DOI：
10.1016/j.jmoldx.2017.01.011
发表时间：
2017-05
期刊：
The Journal of molecular diagnostics : JMD
影响因子：
--
作者：
Jennings LJ;Arcila ME;Corless C;Kamel-Reid S;Lubin IM;Pfeifer J;Temple-Smolkin RL;Voelkerding KV;Nikiforova MN
通讯作者：
Nikiforova MN
影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
Downing, James R.
基于下一代测序的急性髓系白血病移植后监测可识别复发风险高的患者
影响因子：
20.3
作者：
Kim, TaeHyung;Moon, Joon Ho;Kim, Dennis Dong Hwan
通讯作者：
Kim, Dennis Dong Hwan
影响因子：
3.9
作者：
Mannelli F
通讯作者：
Mannelli F