Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Department of Internal Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Nat Med. 2018 Dec;24(12):1867-1876. doi: 10.1038/s41591-018-0269-2. Epub 2018 Dec 6.
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.
多发性骨髓瘤是一种浆细胞恶性肿瘤，是第二常见的血液癌。尽管进行了广泛的研究，但疾病异质性的特征描述很差，这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 40 名个体沿着多发性骨髓瘤进展谱的异质性，包括 11 名健康对照者，证明了个体间的高度可变性，可以通过已知的多发性骨髓瘤驱动因素和其他潜在因素的表达来解释。我们确定了 29 名多发性骨髓瘤患者中有 10 名患者存在广泛的亚克隆结构。在无症状的早期疾病患者和治疗后有微小残留疾病的患者中，我们检测到罕见的肿瘤浆细胞，其分子特征与活动性骨髓瘤相似，这可能对个性化治疗有影响。对罕见循环肿瘤细胞的单细胞分析可实现准确的液体活检和恶性浆细胞的检测，从而反映骨髓疾病。我们的工作建立了单细胞 RNA 测序，用于剖析血液恶性肿瘤，并对有症状和无症状患者的肿瘤细胞进行详细的分子特征描述。
