A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia.
A novel deep targeted sequencing method for minimal residual disease monitoring in acute myeloid leukemia.
复制标题
DOI：
10.3324/haematol.2018.194712
复制
发表时间：
2019-03
期刊：
影响因子：
10.1
通讯作者：
Ayala R
中科院分区：
文献类型：
--
作者：
Onecha E;Linares M;Rapado I;Ruiz-Heredia Y;Martinez-Sanchez P;Cedena T;Pratcorona M;Oteyza JP;Herrera P;Barragan E;Montesinos P;Vela JAG;Magro E;Anguita E;Figuera A;Riaza R;Martinez-Barranco P;Sanchez-Vega B;Nomdedeu J;Gallardo M;Martinez-Lopez J;Ayala R
获得微小残留病阴性状态的急性髓系白血病患者中，有很高比例的患者最终复发，因为标准方法仍未发现一部分病理克隆。我们设计并验证了一种高通量测序方法，用于对带有NPM1、IDH1/2和/或Flt3-单核苷酸变体突变的细胞克隆类型进行最小残留疾病评估。为了临床验证，对63名完全缓解患者的106份随访样本进行了测序研究，评估了在诊断时检测到的突变水平。通过生存分析确定测序、多参数流式细胞术或定量聚合酶链式反应分析对微小残留病状态的预测价值。该测序方法对单核苷酸变异的敏感性为10−4，对插入/缺失的敏感性为10−5，可用于携带任何突变的急性髓系白血病患者(在我们的诊断数据集中为86%)。测序确定的最小残留病阳性状态与较低的无病生存率(风险比3.4，P=0.005)和较低的总生存率(风险比4.2，P<；0.001)相关。多因素分析显示，测序确定的微小残留病阳性状态是与死亡风险相关的独立因素(危险比4.54，P=0.005)，也是唯一与复发风险相关的独立因素(危险比3.76，P=0.012)。这种基于测序的方法简化和标准化了最小残留病的评估，在急性髓系白血病中具有很高的适用性。它也是对基于流式细胞术和定量聚合酶链式反应的急性髓系白血病患者预后预测的改进，并可纳入临床设置和临床试验。
A high proportion of patients with acute myeloid leukemia who achieve minimal residual disease negative status ultimately relapse because a fraction of pathological clones remains undetected by standard methods. We designed and validated a high-throughput sequencing method for minimal residual disease assessment of cell clonotypes with mutations of NPM1, IDH1/2 and/or FLT3-single nucleotide variants. For clinical validation, 106 follow-up samples from 63 patients in complete remission were studied by sequencing, evaluating the level of mutations detected at diagnosis. The predictive value of minimal residual disease status by sequencing, multiparameter flow cytometry, or quantitative polymerase chain reaction analysis was determined by survival analysis. The sequencing method achieved a sensitivity of 10−4 for single nucleotide variants and 10−5 for insertions/deletions and could be used in acute myeloid leukemia patients who carry any mutation (86% in our diagnostic data set). Sequencing–determined minimal residual disease positive status was associated with lower disease-free survival (hazard ratio 3.4, P=0.005) and lower overall survival (hazard ratio 4.2, P<0.001). Multivariate analysis showed that minimal residual disease positive status determined by sequencing was an independent factor associated with risk of death (hazard ratio 4.54, P=0.005) and the only independent factor conferring risk of relapse (hazard ratio 3.76, P=0.012). This sequencing-based method simplifies and standardizes minimal residual disease evaluation, with high applicability in acute myeloid leukemia. It is also an improvement upon flow cytometry- and quantitative polymerase chain reaction-based prediction of outcomes of patients with acute myeloid leukemia and could be incorporated in clinical settings and clinical trials.
登录
查看更多内容
影响因子：
12.3
作者：
McLaren W;Gil L;Hunt SE;Riat HS;Ritchie GR;Thormann A;Flicek P;Cunningham F
通讯作者：
Cunningham F
影响因子：
3.9
作者：
Roloff GW;Lai C;Hourigan CS;Dillon LW
通讯作者：
Dillon LW
影响因子：
51.1
作者：
Rubnitz, Jeffrey E.;Inaba, Hiroto;Dahl, Gary;Ribeiro, Raul C.;Bowman, W. Paul;Taub, Jeffrey;Pounds, Stanley;Razzouk, Bassem I.;Lacayo, Norman J.;Cao, Xueyuan;Meshinchi, Soheil;Degar, Barbara;Airewele, Gladstone;Raimondi, Susana C.;Onciu, Mihaela;Coustan-Smith, Elaine;Downing, James R.;Leung, Wing;Pui, Ching-Hon;Campana, Dario
通讯作者：
Campana, Dario
DOI：
10.1182/asheducation-2016.1.356
发表时间：
2016-12-01
影响因子：
3
作者：
Ossenkoppele, Gert;Schuurhuis, Gerrit Jan
通讯作者：
Schuurhuis, Gerrit Jan
影响因子：
20.3
作者：
Jourdan, Eric;Boissel, Nicolas;Dombret, Herve
通讯作者：
Dombret, Herve