Tumor cells in light-chain amyloidosis and myeloma show distinct transcriptional rewiring of normal plasma cell development

Daniel Alameda, Ibai Goicoechea, Marco Vicari, Elena Arriazu, Alice Nevone, Sara Rodríguez, Marta Lasa, Noemi Puig, Maria-Teresa Cedena, Diego Alignani, Sonia Garate, David Lara-Astiaso, Amaia Vilas-Zornoza, Sarai Sarvide, Enrique M Ocio, Ramón Lecumberri, Alfonso Garcia de Coca, Jorge Labrador, Maria-Esther Gonzalez, Luis PalomeraMercedes Gironella, Valentin Cabañas, Maria Casanova, Albert Oriol, Isabel Krsnik, Albert Pérez-Montaña, Javier de la Rubia, Jose-Enrique de la Puerta, Felipe de Arriba, Vito Michele Fazio, Joaquin Martinez-Lopez, Juan-José Lahuerta, Maria-Victoria Mateos, Maria D Odero, Felipe Prosper, Assaf Weiner, Ido Amit, Mario Nuvolone, Jesus F. F San-Miguel, Bruno Paiva

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1583-1589
Number of pages7
JournalBlood
Volume138
Issue number17
Early online date16 Jun 2021
DOIs
Publication statusPublished - 28 Oct 2021

Funding

Publisher Copyright: © 2021 American Society of Hematology

All Science Journal Classification (ASJC) codes

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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