Department of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
The Key Laboratory for Human Disease Gene Study of Sichuan Province and Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Elife. 2022 Oct 31;11:e75340. doi: 10.7554/eLife.75340.
Multiple myeloma (MM) accounts for ~10% of all haematologic malignancies. Little is known about high intratumour heterogeneities in patients stratified by the Revised International Staging System (R-ISS). Herein, we constructed a single-cell transcriptome atlas to compare differential expression patterns among stages. We found that a novel cytotoxic plasma cell (PC) population exhibited with NKG7 positive was obviously enriched in stage II patients. Additionally, a malignant PC population with significantly elevated expression of MKI67 and PCNA was associated with unfavourable prognosis and Epstein-Barr virus (EBV) infection in our collected samples. Moreover, ribonucleotide reductase regulatory subunit M2 (RRM2) was found and verified to promote proliferation of MM cell lines, suggesting RRM2 may serve as a detrimental marker in MM. The percentages of CD8 T cells and NKT cells decreased along with R-ISS stages, reflecting the plasticity of the tumour immune microenvironment. Importantly, their crosstalks with myeloid cells and PC identified several potential immunotargets such as SIRPA-CD47 and CD74-MIF, respectively. Collectively, this study provided an R-ISS-related single-cell MM atlas and revealed the clinical significance of novel PC clusters, as well as potential immunotargets in MM progression.
多发性骨髓瘤（MM）约占所有血液系统恶性肿瘤的 10%。对于根据修订后的国际分期系统（R-ISS）分层的患者中肿瘤内异质性较高的情况知之甚少。在此，我们构建了一个单细胞转录组图谱，以比较不同阶段之间的差异表达模式。我们发现，一种新型的具有 NKG7 阳性的细胞毒性浆细胞（PC）群体在 II 期患者中明显富集。此外，在我们收集的样本中，一种恶性 PC 群体显著上调了 MKI67 和 PCNA 的表达，与不良预后和 EBV 感染相关。此外，发现并验证了核苷酸还原酶调节亚基 M2（RRM2）可促进 MM 细胞系的增殖，表明 RRM2 可能是 MM 中的有害标志物。随着 R-ISS 阶段的进展，CD8 T 细胞和 NKT 细胞的比例下降，反映了肿瘤免疫微环境的可塑性。重要的是，它们与髓样细胞和 PC 的相互作用分别确定了几个潜在的免疫靶点，如 SIRPA-CD47 和 CD74-MIF。总之，这项研究提供了一个与 R-ISS 相关的单细胞 MM 图谱，并揭示了新型 PC 簇以及 MM 进展中潜在免疫靶点的临床意义。
Zotero 插件
