Multiple myeloma, a plasma cell malignancy, is the second most common blood cancer. Despite extensive research, disease heterogeneity is poorly characterized, hampering efforts for early diagnosis and improved treatments. Here, we apply single cell RNA sequencing to study the heterogeneity of 40 individuals along the multiple myeloma progression spectrum, including 11 healthy controls, demonstrating high interindividual variability that can be explained by expression of known multiple myeloma drivers and additional putative factors. We identify extensive subclonal structures for 10 of 29 individuals with multiple myeloma. In asymptomatic individuals with early disease and in those with minimal residual disease post-treatment, we detect rare tumor plasma cells with molecular characteristics similar to those of active myeloma, with possible implications for personalized therapies. Single cell analysis of rare circulating tumor cells allows for accurate liquid biopsy and detection of malignant plasma cells, which reflect bone marrow disease. Our work establishes single cell RNA sequencing for dissecting blood malignancies and devising detailed molecular characterization of tumor cells in symptomatic and asymptomatic patients.

中文翻译：

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有症状和无症状骨髓瘤中浆细胞异质性的单细胞解剖。

多发性骨髓瘤是一种浆细胞恶性肿瘤，是第二常见的血癌。尽管进行了广泛的研究，但疾病异质性的特征很差，阻碍了早期诊断和改进治疗的努力。在这里，我们应用单细胞 RNA 测序来研究多发性骨髓瘤进展谱中 40 名个体的异质性，其中包括 11 名健康对照，证明了高个体间变异性，这可以通过已知多发性骨髓瘤驱动因素和其他推定因素的表达来解释。我们为 29 名多发性骨髓瘤患者中的 10 名确定了广泛的亚克隆结构。在早期疾病的无症状个体和治疗后具有微小残留疾病的个体中，我们检测到分子特征与活动性骨髓瘤相似的罕见肿瘤浆细胞，可能对个性化治疗产生影响。罕见循环肿瘤细胞的单细胞分析允许准确的液体活检和检测恶性浆细胞，这反映了骨髓疾病。我们的工作建立了用于解剖血液恶性肿瘤的单细胞 RNA 测序，并设计了有症状和无症状患者肿瘤细胞的详细分子特征。