TY - JOUR
T1 - Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development
AU - Alameda, Daniel
AU - Goicoechea, Ibai
AU - Vicari, Marco
AU - Arriazu, Elena
AU - Nevone, Alice
AU - Rodríguez, Sara
AU - Lasa, Marta
AU - Puig, Noemi
AU - Cedena, Maria-Teresa
AU - Alignani, Diego
AU - Garate, Sonia
AU - Lara-Astiaso, David
AU - Vilas-Zornoza, Amaia
AU - Sarvide, Sarai
AU - Ocio, Enrique M
AU - Lecumberri, Ramón
AU - Garcia de Coca, Alfonso
AU - Labrador, Jorge
AU - Gonzalez, Maria-Esther
AU - Palomera, Luis
AU - Gironella, Mercedes
AU - Cabañas, Valentin
AU - Casanova, Maria
AU - Oriol, Albert
AU - Krsnik, Isabel
AU - Pérez-Montaña, Albert
AU - de la Rubia, Javier
AU - de la Puerta, Jose-Enrique
AU - de Arriba, Felipe
AU - Fazio, Vito Michele
AU - Martinez-Lopez, Joaquin
AU - Lahuerta, Juan-José
AU - Mateos, Maria-Victoria
AU - Odero, Maria D
AU - Prosper, Felipe
AU - Weiner, Assaf
AU - Amit, Ido
AU - Nuvolone, Mario
AU - San-Miguel, Jesus F. F
AU - Paiva, Bruno
PY - 2021/10/28
Y1 - 2021/10/28
N2 - Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation–related TPs are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies.
AB - Although light-chain amyloidosis (AL) and multiple myeloma (MM) are characterized by tumor plasma cell (PC) expansion in bone marrow (BM), their clinical presentation differs. Previous attempts to identify unique pathogenic mechanisms behind such differences were unsuccessful, and no studies have investigated the differentiation stage of tumor PCs in patients with AL and MM. We sought to define a transcriptional atlas of normal PC development in secondary lymphoid organs (SLOs), peripheral blood (PB), and BM for comparison with the transcriptional programs (TPs) of tumor PCs in AL, MM, and monoclonal gammopathy of undetermined significance (MGUS). Based on bulk and single-cell RNA sequencing, we observed 13 TPs during transition of normal PCs throughout SLOs, PB, and BM. We further noted the following: CD39 outperforms CD19 to discriminate newborn from long-lived BM-PCs; tumor PCs expressed the most advantageous TPs of normal PC differentiation; AL shares greater similarity to SLO-PCs whereas MM is transcriptionally closer to PB-PCs and newborn BM-PCs; patients with AL and MM enriched in immature TPs had inferior survival; and protein N-linked glycosylation–related TPs are upregulated in AL. Collectively, we provide a novel resource to understand normal PC development and the transcriptional reorganization of AL and other monoclonal gammopathies.
UR - http://www.scopus.com/inward/record.url?scp=85117749922&partnerID=8YFLogxK
U2 - 10.1182/blood.2020009754
DO - 10.1182/blood.2020009754
M3 - Article
SN - 0006-4971
VL - 138
SP - 1583
EP - 1589
JO - Blood
JF - Blood
IS - 17
ER -