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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.
Fuente: Blood . 2021 Oct 28;138(17):1583-1589
Editorial: American Society of Hematology
Año de publicación: 2021
Nº de páginas: 7
Tipo de publicación: Artículo de Revista
DOI: 10.1182/blood.2020009754
ISSN: 0006-4971,1528-0020
Url de la publicación: https://www.doi.org/10.1182/blood.2020009754
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ALAMEDA, DANIEL
GOICOECHEA, IBAI
VICARI, MARCO
ARRIAZU, ELENA
NEVONE, ALICE
RODRIGUEZ, SARA
LASA, MARTA
PUIG, NOEMI
CEDENA, MARIA TERESA
ALIGNANI, DIEGO
GARATE, SONIA
LARA-ASTIASO, DAVID
VILAS-ZORNOZA, AMAIA
SARVIDE, SARAI
ENRIQUE MARIA OCIO SAN MIGUEL
LECUMBERRI, RAMON
GARCIA DE COCA, ALFONSO
LABRADOR, JORGE
GONZALEZ, MARIA-ESTHER
PALOMERA, LUIS
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