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<p>Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells. Minimal residual disease (MRD) assessment holds prognostic significance in both newly diagnosed and relapsed MM patients throughout the disease course. PCR-based targeted next-generation sequencing (NGS) methods face limitations in MRD monitoring due to somatic hypermutation (SHM) in MM. This study compares RNA-seq with the targeted IGH-CDR3-DNA-NGS method to identify more sensitive and convenient MRD monitoring techniques. We analyzed 125 samples from 35 MM patients and compared with 42 B-ALL patients, using MiXCR software for sequencing data processing. RNA-seq detected clonal immunoglobulin (IG) sequences in all bone marrow (BM) and peripheral blood (PB) initial samples with a sensitivity of 10<sup>-6</sup>, outperforming targeted-NGS, which missed some detections. The SHM rate was higher in targeted-NGS-negative samples (9.98%) compared to positive ones (7.27%). Clonal IG gene expression in MM was significantly higher than in B-ALL. Additionally, MRD-negative PB samples identified via RNA-seq and IG tag sequence correlated with improved survival. In conclusion, RNA-seq surpasses targeted-NGS in MRD monitoring for MM patients, providing comprehensive genetic information that aids in identifying specific IG gene expression patterns. Utilizing RNA-seq for MRD detection in PB samples effectively predicts prognosis.</p>

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Using RNA-seq for detecting MRD in multiple myeloma: high sensitivity and prognostic value

  • 期刊论文

  • 发表日期：

    2025年10月24日

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  • Yuyue Ren,
  • Ming Liu,
  • Jiancheng Fang,
  • Lianjie Wang,
  • Yanming Xue,
  • Weiwei Zhao,
  • Juan Liu,
  • Liqian Yu,
  • Yinglan Jin,
  • Liyan Chen,
  • Yaoyao Tian,
  • Xinyu Gao,
  • Xiaomin Zhang,
  • Biqing Han,
  • Dandan Yao,
  • Yan Song,
  • Xi Chen,
  • Fang Wang,
  • Xiaoli Ma,
  • Hongxing Liu,
  • Wei Wang

摘要

Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of plasma cells. Minimal residual disease (MRD) assessment holds prognostic significance in both newly diagnosed and relapsed MM patients throughout the disease course. PCR-based targeted next-generation sequencing (NGS) methods face limitations in MRD monitoring due to somatic hypermutation (SHM) in MM. This study compares RNA-seq with the targeted IGH-CDR3-DNA-NGS method to identify more sensitive and convenient MRD monitoring techniques. We analyzed 125 samples from 35 MM patients and compared with 42 B-ALL patients, using MiXCR software for sequencing data processing. RNA-seq detected clonal immunoglobulin (IG) sequences in all bone marrow (BM) and peripheral blood (PB) initial samples with a sensitivity of 10-6, outperforming targeted-NGS, which missed some detections. The SHM rate was higher in targeted-NGS-negative samples (9.98%) compared to positive ones (7.27%). Clonal IG gene expression in MM was significantly higher than in B-ALL. Additionally, MRD-negative PB samples identified via RNA-seq and IG tag sequence correlated with improved survival. In conclusion, RNA-seq surpasses targeted-NGS in MRD monitoring for MM patients, providing comprehensive genetic information that aids in identifying specific IG gene expression patterns. Utilizing RNA-seq for MRD detection in PB samples effectively predicts prognosis.