Co-evolution of tumor and immune cells during progression of multiple myeloma

Ruiyang Liu, Qingsong Gao, Steven M. Foltz, Jared S. Fowles, Lijun Yao, Julia Tianjiao Wang, Song Cao, Hua Sun, Michael C. Wendl, Sunantha Sethuraman, Amila Weerasinghe, Michael P. Rettig, Erik P. Storrs, Christopher J. Yoon, Matthew A. Wyczalkowski, Joshua F. McMichael, Daniel R. Kohnen, Justin King, Scott R. Goldsmith, Julie O’Neal, Robert S. Fulton, Catrina C. Fronick, Timothy J. Ley, Reyka G. Jayasinghe, Mark A. Fiala, Stephen T. Oh, John F. DiPersio, Ravi Vij () and Li Ding ()
Additional contact information
Ruiyang Liu: Washington University in St. Louis
Qingsong Gao: Washington University in St. Louis
Steven M. Foltz: Washington University in St. Louis
Jared S. Fowles: Washington University in St. Louis
Lijun Yao: Washington University in St. Louis
Julia Tianjiao Wang: Washington University in St. Louis
Song Cao: Washington University in St. Louis
Hua Sun: Washington University in St. Louis
Michael C. Wendl: Washington University in St. Louis
Sunantha Sethuraman: Washington University in St. Louis
Amila Weerasinghe: Washington University in St. Louis
Michael P. Rettig: Washington University in St. Louis
Erik P. Storrs: Washington University in St. Louis
Christopher J. Yoon: Washington University in St. Louis
Matthew A. Wyczalkowski: Washington University in St. Louis
Joshua F. McMichael: Washington University in St. Louis
Daniel R. Kohnen: Washington University in St. Louis
Justin King: Washington University in St. Louis
Scott R. Goldsmith: Washington University in St. Louis
Julie O’Neal: Washington University in St. Louis
Robert S. Fulton: Washington University in St. Louis
Catrina C. Fronick: Washington University in St. Louis
Timothy J. Ley: Washington University in St. Louis
Reyka G. Jayasinghe: Washington University in St. Louis
Mark A. Fiala: Washington University in St. Louis
Stephen T. Oh: Washington University in St. Louis
John F. DiPersio: Washington University in St. Louis
Ravi Vij: Washington University in St. Louis
Li Ding: Washington University in St. Louis

Nature Communications, 2021, vol. 12, issue 1, 1-18

Abstract: Abstract Multiple myeloma (MM) is characterized by the uncontrolled proliferation of plasma cells. Despite recent treatment advances, it is still incurable as disease progression is not fully understood. To investigate MM and its immune environment, we apply single cell RNA and linked-read whole genome sequencing to profile 29 longitudinal samples at different disease stages from 14 patients. Here, we collect 17,267 plasma cells and 57,719 immune cells, discovering patient-specific plasma cell profiles and immune cell expression changes. Patients with the same genetic alterations tend to have both plasma cells and immune cells clustered together. By integrating bulk genomics and single cell mapping, we track plasma cell subpopulations across disease stages and find three patterns: stability (from precancer to diagnosis), and gain or loss (from diagnosis to relapse). In multiple patients, we detect “B cell-featured” plasma cell subpopulations that cluster closely with B cells, implicating their cell of origin. We validate AP-1 complex differential expression (JUN and FOS) in plasma cell subpopulations using CyTOF-based protein assays, and integrated analysis of single-cell RNA and CyTOF data reveals AP-1 downstream targets (IL6 and IL1B) potentially leading to inflammation regulation. Our work represents a longitudinal investigation for tumor and microenvironment during MM progression and paves the way for expanding treatment options.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22804-x

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DOI: 10.1038/s41467-021-22804-x

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