多发性骨髓瘤是一种无法治愈的浆细胞恶性肿瘤，存活率低，通常使用免疫调节药物（iMiDs）和蛋白酶体抑制剂（PIs）进行治疗。恶性浆细胞很快对这些药物产生耐药性，导致复发和抵抗性克隆的不受控制的增长。通过全基因组测序（WGS）和RNA测序（RNA-seq）研究，已经鉴定出不同的高风险易位、拷贝数、突变和转录标记物。其中一个标记物，PHF19，在表观遗传水平上调节细胞周期和其他过程，并且已经使用RNA测序进行了研究。在本研究中，我们使用了大规模（325,025个细胞和49名患者）的单细胞多组学数据集，分别为每个细胞进行了ATAC-seq和RNA-seq定量，并为每个患者提供了配对的基因组概况。我们确定了一种与骨髓瘤进展相关的浆细胞亚型，我们将其称为复发/难治性浆细胞（RRPCs）。这些细胞与1q易位、TP53突变以及PHF19的高表达相关。我们还确定了这些细胞中细胞周期抑制剂的下游调节，1q上转录因子（TF）PBX1的可能调节，以及PHF19可能主要通过这一细胞亚群发挥作用。

Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers have been identified. One of these markers, PHF19 , epigenetically regulates cell cycle and other processes and has already been studied using RNA-seq. In this study a massive (325,025 cells and 49 patients) single cell multiomic dataset was generated with jointly quantified ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identified an association between one plasma cell subtype with myeloma progression that we have called relapsed/refractory plasma cells (RRPCs). These cells are associated with 1q alterations, TP53 mutations, and higher expression of PHF19 . We also identified downstream regulation of cell cycle inhibitors in these cells, possible regulation of the transcription factor (TF) PBX1 on 1q, and determined that PHF19 may be acting primarily through this subset of cells.