TY - JOUR
T1 - Co-evolution of tumor and immune cells during progression of multiple myeloma
AU - Liu, Ruiyang
AU - Gao, Qingsong
AU - Foltz, Steven M.
AU - Fowles, Jared S.
AU - Yao, Lijun
AU - Wang, Julia Tianjiao
AU - Cao, Song
AU - Sun, Hua
AU - Wendl, Michael C.
AU - Sethuraman, Sunantha
AU - Weerasinghe, Amila
AU - Rettig, Michael P.
AU - Storrs, Erik P.
AU - Yoon, Christopher J.
AU - Wyczalkowski, Matthew A.
AU - McMichael, Joshua F.
AU - Kohnen, Daniel R.
AU - King, Justin
AU - Goldsmith, Scott R.
AU - O’Neal, Julie
AU - Fulton, Robert S.
AU - Fronick, Catrina C.
AU - Ley, Timothy J.
AU - Jayasinghe, Reyka G.
AU - Fiala, Mark A.
AU - Oh, Stephen T.
AU - DiPersio, John F.
AU - Vij, Ravi
AU - Ding, Li
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12/1
Y1 - 2021/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85105518537&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-22804-x
DO - 10.1038/s41467-021-22804-x
M3 - Article
C2 - 33963182
AN - SCOPUS:85105518537
SN - 2041-1723
VL - 12
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 2559
ER -