RT Journal Article
T1 Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development
A1 Alameda, Daniel
A1 Goicoechea, Ibai
A1 Vicari, Marco
A1 Arriazu, Elena
A1 Nevone, Alice
A1 Rodriguez, Sara
A1 Lasa, Marta
A1 Puig, Noemi
A1 Teresa Cedena, Maria
A1 Alignani, Diego
A1 Garate, Sonia
A1 Lara-Astiaso, David
A1 Vilas-Zornoza, Amaia
A1 Sarvide, Sarai
A1 Ocio, Enrique M.
A1 Lecumberri, Ramon
A1 Garcia de Coca, Alfonso
A1 Labrador, Jorge
A1 Gonzalez, Maria-Esther
A1 Palomera, Luis
A1 Gironella, Mercedes
A1 Cabanas, Valentin
A1 Casanova, Maria
A1 Oriol, Albert
A1 Krsnik, Isabel
A1 Perez-Montana, Albert
A1 de la Rubia, Javier
A1 de la Puerta, Jose-Enrique
A1 de Arriba, Felipe
A1 Michele Fazio, Vito
A1 Martinez-Lopez, Joaquin
A1 Lahuerta, Juan-Jose
A1 Mateos, Maria-Victoria
A1 Odero, Maria-Dolores
A1 Prosper, Felipe
A1 Weiner, Assaf
A1 Amit, Ido
A1 Nuvolone, Mario
A1 San Miguel, Jesus F.
A1 Paiva, Bruno
K1 Multiple-myeloma
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.
PB Amer soc hematology
SN 0006-4971
YR 2021
FD 2021-10-28
LK https://hdl.handle.net/10668/26713
UL https://hdl.handle.net/10668/26713
LA en
DS RISalud
RD Apr 11, 2025