基于ctdna的最小残留疾病检测在新诊断的外周t细胞淋巴瘤中的临床意义:一项单中心队列研究

IF 8.2 2区 生物学 Q1 CELL BIOLOGY
Jin-Hua Liang, Wei Hua, Hua Yin, Yue Li, Xin-Yi Zhang, Jun-Heng Liang, Liu-Qing Zhu, Rui Gao, Chen-Xuan Wang, Yang Shao, Bi-Hui Pan, Xin-Yu Zhang, Jia-Zhu Wu, Qiu-Xiang Ou, Jian-Yong Li, Hao-Rui Shen, Li Wang, Wei Xu
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引用次数: 0

摘要

循环肿瘤DNA (ctDNA)被认为是一种有前景的肿瘤特异性生物标志物,但其在外周血T细胞淋巴瘤(PTCL)中的分子特征尚未得到很好的探索。我们研究了液体活检在均匀治疗的PTCL队列中的翻译意义(N=64)。我们的研究发现,预处理ctDNA负荷与临床危险因素密切相关,并被确定为无进展生存期和总生存期的优越预测因子。虽然46.9%的患者在治疗结束时达到完全缓解(EOT),但只有25.9%的患者达到阴性最小残留病(MRDend-),并表现出良好的预后。这些发现表明,EOT时的MRD状态可能是PTCL患者疾病进展和复发的关键因素。此外,最常改变的基因被鉴定为TET2(6.7%)、DNMT3A(48.5%)、RHOA(27.3%)和TP53(15.2%),这些基因未被一线chop样方案清除。最重要的是,在诱导治疗和随访期间,所有组织学亚型的PTCL患者都显示出克隆进化。这些发现支持EOT MRD状态可以作为PTCL患者重要的预后标志物,并明确了探索和选择针对TET2/DNMT3A/RHOA突变的新药与PTCL患者常规治疗相结合的方向。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical implications of ctDNA-based minimal residual disease detection in newly diagnosed peripheral T-cell lymphoma: a single-center cohort study.

Circulating tumor DNA (ctDNA) has been recognized as a promising tumor-specific biomarker, but its molecular features in peripheral T cell lymphoma (PTCL) have not been well explored. We investigated the translational significance of liquid biopsy in a uniformly treated PTCL cohort (N=64). Our study found that pretreatment ctDNA burden was strongly associated with clinical risk factors and identified as a superior predictor of progression-free survival and overall survival. Although 46.9% of patients achieved complete response at the end of therapy (EOT), only 25.9% achieved negative minimal residual disease (MRDend-) and demonstrated superior prognosis. These findings suggests that MRD status at EOT may be a critical factor in disease progression and recurrence for PTCL patients. Additionally, the most frequently altered genes were identified as TET2 (6.7%), DNMT3A (48.5%), RHOA (27.3%), and TP53 (15.2%), which were not cleared by first-line CHOP-like regimens. Most importantly, clonal evolution was displayed during induction therapy and follow-up across all histological subtypes of PTCL patients.These findings support that EOT MRD status could serve as an important prognostic marker for PTCL patients and clear the direction of exploration and selection the new drugs particularly targeted to TET2/DNMT3A/RHOA mutation integrating with conventional treatments for PTCL patients.

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来源期刊
CiteScore
11.00
自引率
0.00%
发文量
180
期刊介绍: Cell Communication and Signaling (CCS) is a peer-reviewed, open-access scientific journal that focuses on cellular signaling pathways in both normal and pathological conditions. It publishes original research, reviews, and commentaries, welcoming studies that utilize molecular, morphological, biochemical, structural, and cell biology approaches. CCS also encourages interdisciplinary work and innovative models, including in silico, in vitro, and in vivo approaches, to facilitate investigations of cell signaling pathways, networks, and behavior. Starting from January 2019, CCS is proud to announce its affiliation with the International Cell Death Society. The journal now encourages submissions covering all aspects of cell death, including apoptotic and non-apoptotic mechanisms, cell death in model systems, autophagy, clearance of dying cells, and the immunological and pathological consequences of dying cells in the tissue microenvironment.
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