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Large Single-Cell RNA-Sequencing Cohort Sheds Light on Precursor Conditions to Multiple Myeloma

By: Emily Rhode
Posted: Monday, January 30, 2023

At the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 102), Junko Tsuji, PhD, of the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, and colleagues shared their results from the largest single-cell RNA sequencing cohort of tumor samples from patients with monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma. Their research identified differences in dysregulation of gene expression across disease stages and revealed unique understanding of plasma cell malignancy.

“Observations gleaned from this data set could be used to nominate novel targets and prioritize target validation for the development of novel therapeutics for the treatment or prevention of [multiple myeloma],” the investigators concluded.

In this study, 245 bone marrow tissue samples were taken from patients with MGUS (n = 36), patients with smoldering multiple myeloma (n = 136), patients with multiple myeloma (n = 37), and healthy donors (n = 25). Sequencing was performed on a total of 1,318,218 plasma cells, of which 960,998 were malignant and 357,220 were normal. The investigators then compared expression levels between normal and malignant plasma cells to identify differentially expressed genes in tumors and the frequency of gene dysregulation within the cohort.

Analysis showed for the first time the frequent downregulation of several genes, including one associated with cell migration and four associated with protein folding and regulation of endoplasmic reticulum stress. Additionally, PDK1 was found to be frequently downregulated in malignant plasma cells. The authors noted that this may suggest a difference in the balance between oxidative phosphorylation and aerobic glycolysis between malignant and normal plasma cells. Upregulation of MYC and CD47 was more frequent in patients with smoldering multiple myeloma, whereas upregulation of several genes, including DDX21, SLAMF7, TXNDC11, PIM2, and IRF9, was more frequent in patients with multiple myeloma.

Disclosure: For full disclosures of the study authors, visit

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