1. Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development
- Author
-
Javier de la Rubia, Maria Victoria Mateos, David Lara-Astiaso, Amaia Vilas-Zornoza, Joaquin Martinez-Lopez, Ramón Lecumberri, Sara Rodriguez, Marco Vicari, Sonia Garate, María Teresa Cedena, Ibai Goicoechea, Assaf Weiner, Luis Palomera, María José Casanova, Sarai Sarvide, Vito Michele Fazio, Jose Enrique de la Puerta, Alfonso García de Coca, Jesús F. San Miguel, Maria Esther González, Diego Alignani, Alice Nevone, Noemi Puig, Albert Oriol, Ido Amit, Felipe de Arriba, Bruno Paiva, María D. Odero, Valentin Cabañas, Isabel Krsnik, Felipe Prosper, Enrique M. Ocio, Daniel Alameda, Marta Lasa, Elena Arriazu, Mercedes Gironella, Jorge Labrador, Albert Pérez-Montaña, Juan J. Lahuerta, and Mario Nuvolone
- Subjects
Adult ,Plasma Cells ,Immunology ,Biology ,Plasma cell ,Immunoglobulin light chain ,Biochemistry ,CD19 ,CME article ,Tumor Cells, Cultured ,medicine ,Humans ,Immunoglobulin Light-chain Amyloidosis ,Free Research Articles ,Multiple myeloma ,Lymphoid Neoplasia ,Amyloidosis ,Cell Biology ,Hematology ,medicine.disease ,humanities ,medicine.anatomical_structure ,Monoclonal ,biology.protein ,Cancer research ,Brief Reports ,Bone marrow ,Multiple Myeloma ,Transcriptome ,Monoclonal gammopathy of undetermined significance - Abstract
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.
- Published
- 2021