急性髓性白血病中高灵敏度 flt3-itd 检测所揭示的克隆动态和复发风险。

IF 7.1 1区 医学 Q1 PATHOLOGY
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引用次数: 0

摘要

检测低水平疾病的能力是我们了解急性髓性白血病(AML)克隆异质性和残留疾病的关键,这些疾病无法通过传统检测方法检测,并为复发埋下了隐患。我们开发了一种高灵敏度下一代测序(HS-NGS)临床检测方法,能够可靠地检测出低水平(1x10-5)的 FLT3-ITD,这是急性髓性白血病中一种常见的、可作为治疗靶点且与预后相关的突变。通过对 62 例患者在初次诊断和/或临床随访(平均随访 22 个月)时的 289 份纵向样本应用该检测方法,我们揭示了 FLT3-ITD 亚克隆在诊断时的频繁出现,并证明当 FLT3-ITD 在诱导后或之后被清除时,复发风险会显著降低。我们对 23 例患者的诊断样本和复发样本进行了配对测序,发现了复发时 FLT3-ITD 克隆演化的更详细模式,而非敏感度较低的检测方法所能检测到的。最后,我们发现连续活检中 ITD 水平的升高是即将复发的先兆。我们的研究结果证实了高灵敏度 FLT3-ITD 检测在临床上的新用途,并拓展了我们对 FLT3-ITD 阳性急性髓细胞白血病克隆动态的认识。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clonal Dynamics and Relapse Risk Revealed by High-Sensitivity FLT3-Internal Tandem Duplication Detection in Acute Myeloid Leukemia

The ability to detect low-level disease is key to our understanding of clonal heterogeneity in acute myeloid leukemia (AML) and residual disease that elude conventional assays and seed relapse. We developed a high-sensitivity next-generation sequencing (HS-NGS) clinical assay, able to reliably detect low levels (1 × 10−5) of FLT3-ITD, a frequent, therapeutically targetable and prognostically relevant mutation in AML. By applying this assay to 289 longitudinal samples from 62 patients at initial diagnosis and/or clinical follow-up (mean follow-up of 22 months), we reveal the frequent occurrence of FLT3-ITD subclones at diagnosis and demonstrate a significantly decreased relapse risk when FLT3-ITD is cleared after induction or thereafter. We perform pairwise sequencing of diagnosis and relapse samples from 23 patients to uncover more detailed patterns of FLT3-ITD clonal evolution at relapse than is detectable by less-sensitive assays. Finally, we show that rising ITD level during consecutive biopsies is a harbinger of impending relapse. Our findings corroborate the emerging clinical utility of high-sensitivity FLT3-ITD testing and expands our understanding of clonal dynamics in FLT3-ITD–positive AML.

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来源期刊
Modern Pathology
Modern Pathology 医学-病理学
CiteScore
14.30
自引率
2.70%
发文量
174
审稿时长
18 days
期刊介绍: Modern Pathology, an international journal under the ownership of The United States & Canadian Academy of Pathology (USCAP), serves as an authoritative platform for publishing top-tier clinical and translational research studies in pathology. Original manuscripts are the primary focus of Modern Pathology, complemented by impactful editorials, reviews, and practice guidelines covering all facets of precision diagnostics in human pathology. The journal's scope includes advancements in molecular diagnostics and genomic classifications of diseases, breakthroughs in immune-oncology, computational science, applied bioinformatics, and digital pathology.
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