多发性骨髓瘤（MM）伴随着对正常浆细胞（PC）蛋白组的改变，导致肿瘤微环境和疾病进展发生改变。了解导致MM进展的后果以及发现可用于临床诊断和作为治疗靶点的新生物标志物具有重要意义。本研究展示了利用单细胞高精度液体活检分析（HDSCA）和成像质谱细胞仪对骨髓瘤的蛋白组学特征进行表征的可行性。在我们的研究中，我们分析了来自七个患者样本（骨髓和外周血）的约87,000个细胞，覆盖了骨髓瘤疾病谱的不同阶段，并利用我们的多重标志物面板对PC分类的临床标记物的表达、额外潜在治疗靶点和肿瘤微环境细胞进行了表征。我们的分析显示，BCMA、ICAM3（CD50）、CD221和CS1（SLAMF7）是各个骨髓瘤阶段中PC上表达最丰富的标记物，其中BCMA、ICAM3和CD221在疾病PC与前体PC之间具有显著的更高表达水平。另外，我们发现在PC由明显的疾病状态转变为前体状态时，CD74、MUM1、CD229、CD44、IGLL5、Cyclin D1、UBA52和CD317的表达水平显著升高。© 2023. Nature Publishing Group UK.

Multiple myeloma (MM) is accompanied by alterations to the normal plasma cell (PC) proteome, leading to changes to the tumor microenvironment and disease progression. There is a great need for understanding the consequences that lead to MM progression and for the discovery of new biomarkers that can aid clinical diagnostics and serve as targets for therapeutics. This study demonstrates the applicability of utilizing the single-cell high-definition liquid biopsy assay (HDSCA) and imaging mass cytometry to characterize the proteomic profile of myeloma. In our study, we analyzed ~87,000 cells from seven patient samples (bone marrow and peripheral blood) across the myeloma disease spectrum and utilized our multiplexed panel to characterize the expression of clinical markers for PC classification, additional potential therapeutic targets, and the tumor microenvironment cells. Our analysis showed BCMA, ICAM3 (CD50), CD221, and CS1 (SLAMF7) as the most abundantly expressed markers on PCs across all myeloma stages, with BCMA, ICAM3, and CD221 having significantly higher expression levels on disease versus precursor PCs. Additionally, we identify significantly elevated levels of expression for CD74, MUM1, CD229, CD44, IGLL5, Cyclin D1, UBA52, and CD317 on PCs from overt disease conditions compared to those from precursor states.© 2023. Nature Publishing Group UK.