文章：

使用携带ABL及目标突变的整合载体标准化AML分子MRD水平

Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest

原文发布日期：10 November 2023

DOI: 10.3390/cancers15225360

类型: Article

开放获取: 是

英文摘要：

Quantitative PCR for specific mutation is being increasingly used in Acute Myeloid Leukemia (AML) to assess Measurable Residual Disease (MRD), allowing for more tailored clinical decisions. To date, standardized molecular MRD is limited to typical NPM1 mutations and core binding factor translocations, with clear prognostic and clinical implications. The monitoring of other identified mutations lacks standardization, limiting its use and incorporation in clinical trials. To overcome this problem, we designed a plasmid bearing both the sequence of the mutation of interest and the ABL reference gene. This allows the use of commercial standards for ABL to determine the MRD response in copy number. We provide technical aspects of this approach as well as our experience with 19 patients with atypical NPM1, RUNX1 and IDH1/2 mutations. In all cases, we demonstrate a correlation between response and copy number. We further demonstrate how copy number monitoring can modulate the clinical management. Taken together, we provide proof of concept of a novel yet simple tool, which allows in-house MRD monitoring for identified mutations, with ABL-based commercial standards. This approach would facilitate large multi-center studies assessing the clinical relevance of selected MRD monitoring.

摘要翻译： 

针对特定突变的定量PCR技术正日益应用于急性髓系白血病（AML）的可测量残留病（MRD）评估，从而实现更为个体化的临床决策。目前，标准化分子MRD检测仅限于典型NPM1突变和核心结合因子易位，这些突变具有明确的预后和临床意义。而其他已识别突变的监测缺乏标准化，限制了其在临床试验中的应用与整合。为解决这一问题，我们设计了一种同时携带目标突变序列和ABL参考基因的质粒。这使得可利用ABL商业标准品以拷贝数形式确定MRD反应。我们详细阐述了该方法的技术细节，并分享了在19例非典型NPM1、RUNX1及IDH1/2突变患者中的应用经验。所有案例均显示治疗反应与拷贝数变化存在相关性。我们进一步论证了拷贝数监测如何优化临床管理策略。综上所述，我们提出了一种新颖而简易的技术方案，通过基于ABL的商业标准品实现对特定突变的院内MRD监测。该方法将有助于开展大规模多中心研究，以评估选择性MRD监测的临床价值。

原文链接：

Standardization of Molecular MRD Levels in AML Using an Integral Vector Bearing ABL and the Mutation of Interest