Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA. A total of 162 newly diagnosed MM patients were screened using 18F-FDG PET/CT and assessed by ultra low-pass whole genome sequencing (ULP-WGS). High cfDNA tumor fraction (ctDNA) levels were correlated with different tumor mass markers, and patients with high ctDNA levels at diagnosis were more likely to present with metabolically active paraskeletal (PS) and extramedullary (EM) lesions. Moreover, we demonstrated that microenvironment cancer-associated fibroblast (CAFs)-mediated inflammation might correlate with high ctDNA levels. Indeed, a high cfDNA TF level at diagnosis predicted a poorer prognosis, independent of R-ISS III and 1q amplification; the inclusion of >12% ctDNA in the current R-ISS risk score enables a better identification of high-risk patients. ctDNA can be a reliable and less invasive marker for disease characterization, and can refine patient risk.
多发性骨髓瘤（MM）是一种浆细胞疾病，其特征为诊断时即存在骨骼受累。近期研究表明，无细胞DNA（cfDNA）能够重现骨髓疾病的异质性。本研究旨在根据疾病分布评估诊断时cfDNA的预后作用，并探究骨髓瘤微环境炎症状态对cfDNA释放的影响。通过18F-FDG PET/CT筛查162例新诊断MM患者，并采用超低通量全基因组测序（ULP-WGS）进行分析。高cfDNA肿瘤分数（ctDNA）水平与不同肿瘤负荷标志物相关，且诊断时ctDNA水平高的患者更易出现代谢活性型骨旁（PS）和髓外（EM）病灶。此外，研究证实肿瘤相关成纤维细胞（CAFs）介导的微环境炎症可能与高ctDNA水平相关。诊断时高cfDNA肿瘤分数可独立于R-ISS III期和1q扩增预测不良预后；将>12% ctDNA纳入现有R-ISS风险评分体系能更精准识别高危患者。ctDNA可作为疾病特征分析的可靠且微创标志物，并能优化患者风险分层。
肿瘤(癌症)患者之家