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Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing

ABSTRACT: Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing

PROVIDER: PRJNA961677 | ENA |

REPOSITORIES: ENA

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Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing

Project description:Myelomatous effusion (ME) is a rare manifestion of extramedullary multiple myeloma (MM) with limited therapeutic options and poor outcomes. To investigate the evolutionary mechanisms of ME, we used single-cell RNA sequencing to assess the transcriptomes of bone marrow, peripheral blood, and pleural effusion/ascites from three patients with ME.

2023-04-26 | GSE230510 | GEO

Identification of evolutionary mechanisms of myelomatous effusion by single-cell RNA sequencing.

Project description:Myelomatous effusion (ME) is a rare manifestation of extramedullary multiple myeloma (MM) with limited therapeutic options and poor outcomes. The molecular mechanisms underlying ME are incompletely understood. We profiled transcriptomes of bone marrow, peripheral blood (PB), and pleural effusion/ascites from 3 patients with ME using single-cell RNA sequencing analysis. We found that ME contained a higher percentage of cytotoxic T cells, whereas PB contained a higher proportion of naive T cells. Malignant cells varied within and between sites and patients in their expression of signatures. We identified a gene module highly expressed in intramedullary and extramedullary plasma cell clusters and defined cell clusters expressing this gene set as extramedullary-initiating cells (EMICs). This gene set was associated with increased cellular proliferation, involved in p53 signaling, and related to poor prognosis in MM. The transcriptional regulators E2F1, YY1, and SMAD1 were activated in EMICs. Leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) was upregulated in extramedullary EMICs. We confirmed that LILRB4 promoted MM cell migration in vitro. This study provided insight into the evolutionary mechanisms of ME and defined EMICs and LILRB4 associated with extramedullary development.

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