Faculty, Staff and Student Publications

Publication Date

6-12-2023

Journal

Cancel Cell

Abstract

Multiple myeloma remains an incurable disease, and the cellular and molecular evolution from precursor conditions, including monoclonal gammopathy of undetermined significance and smoldering multiple myeloma, is incompletely understood. Here, we combine single-cell RNA and B cell receptor sequencing from fifty-two patients with myeloma precursors in comparison with myeloma and normal donors. Our comprehensive analysis reveals early genomic drivers of malignant transformation, distinct transcriptional features, and divergent clonal expansion in hyperdiploid versus non-hyperdiploid samples. Additionally, we observe intra-patient heterogeneity with potential therapeutic implications and identify distinct patterns of evolution from myeloma precursor disease to myeloma. We also demonstrate distinctive characteristics of the microenvironment associated with specific genomic changes in myeloma cells. These findings add to our knowledge about myeloma precursor disease progression, providing valuable insights into patient risk stratification, biomarker discovery, and possible clinical applications.

Keywords

Humans, Multiple Myeloma, Smoldering Multiple Myeloma, Aneuploidy, Biomedical Research, Disease Progression, Tumor Microenvironment

DOI

10.1016/j.ccell.2023.05.007

PMID

37311413

PMCID

PMC10317474

PubMedCentral® Posted Date

June 2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

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