Enhancing prognostic power in multiple myeloma using a plasma cell signature derived from single-cell RNA sequencing. Blood Cancer J 2024 Mar 06;14(1):38
Date
03/06/2024Pubmed ID
38443358Pubmed Central ID
PMC10915134DOI
10.1038/s41408-024-01024-8Scopus ID
2-s2.0-85186929795 (requires institutional sign-in at Scopus site)Abstract
Multiple myeloma (MM) is a heterogenous plasma cell malignancy, for which the established prognostic models exhibit limitations in capturing the full spectrum of outcome variability. Leveraging single-cell RNA-sequencing data, we developed a novel plasma cell gene signature. We evaluated and validated the associations of the resulting plasma cell malignancy (PBM) score with disease state, progression and clinical outcomes using data from five independent myeloma studies consisting of 2115 samples (1978 MM, 65 monoclonal gammopathy of undetermined significance, 35 smoldering MM, and 37 healthy controls). Overall, a higher PBM score was significantly associated with a more advanced stage within the spectrum of plasma cell dyscrasias (all p < 0.05) and a shorter overall survival in MM (hazard ratio, HR = 1.72; p < 0.001). Notably, the prognostic effect of the PBM score was independent of the International Staging System (ISS) and Revised ISS (R-ISS). The downstream analysis further linked higher PBM scores with the presence of cytogenetic abnormalities, TP53 mutations, and compositional changes in the myeloma tumor immune microenvironment. Our integrated analyses suggest the PBM score may provide an opportunity for refining risk stratification and guide decisions on therapeutic approaches to MM.
Author List
Li JR, Arsang-Jang S, Cheng Y, Sun F, D'Souza A, Dhakal B, Hari P, Huang Q, Auer P, Li Y, Urrutia R, Zhan F, Shaughnessy JD Jr, Janz S, Dong J, Cheng CAuthors
Shahram Arsang-Jang Postdoctoral Fellow in the Medicine department at Medical College of WisconsinPaul L. Auer PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin
Anita D'Souza MD Associate Professor in the Medicine department at Medical College of Wisconsin
Binod Dhakal MD Associate Professor in the Medicine department at Medical College of Wisconsin
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin
Raul A. Urrutia MD Center Director, Professor in the Surgery department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
HumansMultiple Myeloma
Paraproteinemias
Plasma Cells
Prognosis
Sequence Analysis, RNA
Tumor Microenvironment
