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

Author:

Alameda Daniel1ORCID,Goicoechea Ibai12ORCID,Vicari Marco1ORCID,Arriazu Elena1,Nevone Alice3,Rodriguez Sara1ORCID,Lasa Marta1,Puig Noemi4ORCID,Cedena Maria Teresa25,Alignani Diego12,Garate Sonia1,Lara-Astiaso David1,Vilas-Zornoza Amaia16ORCID,Sarvide Sarai1,Ocio Enrique M.7ORCID,Lecumberri Ramon1,Garcia de Coca Alfonso8ORCID,Labrador Jorge9,Gonzalez Maria-Esther10,Palomera Luis11,Gironella Mercedes12,Cabañas Valentin13ORCID,Casanova Maria14,Oriol Albert1516ORCID,Krsnik Isabel17ORCID,Perez-Montaña Albert18,de la Rubia Javier19ORCID,de la Puerta Jose-Enrique20ORCID,de Arriba Felipe21,Fazio Vito Michele22,Martinez-Lopez Joaquin25ORCID,Lahuerta Juan-Jose25ORCID,Mateos Maria-Victoria3ORCID,Odero Maria-Dolores1ORCID,Prosper Felipe16ORCID,Weiner Assaf23ORCID,Amit Ido23,Nuvolone Mario3,San Miguel Jesus F.12ORCID,Paiva Bruno12ORCID

Affiliation:

1. Clinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain;

2. Centro de Investigación Biomédica en Red de Oncología (CIBERONC) CB16/12/00369, Pamplona, Spain;

3. Amyloidosis Research and Treatment Center, Foundation IRCCS Policlinico San Matteo, Department of Molecular Medicine, University of Pavia, Pavia, Italy;

4. Centro de Investigación del Cancer, Instituto de Biología Molecular y Celular del Cáncer–Universidad de Salamanca (IBMCC-USAL), Consejo Superior de Investigaciones Científicas (CSIC), Instituto de Investigacion Biomedica de Salamanca (IBSAL), Hospital Universitario de Salamanca, Salamanca, Spain;

5. Centro Nacional de Investigaciones Oncológicas (CNIO), Hospital 12 de Octubre, Universidad Complutense, Madrid, Spain;

6. CIBER-ONC CB16/12/00489, Pamplona, Spain;

7. Hospital Universitario Marqués de Valdecilla (IDIVAL), Universidad de Cantabria, Santander, Spain;

8. Hospital Clínico Universitario de Valladolid, Valladolid, Spain;

9. Hospital Universitario de Burgos, Burgos, Spain;

10. Hospital de Cabueñes, Gijon, Spain;

11. Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain;

12. Hospital Universitari Vall d’Hebron, Barcelona, Spain;

13. Hospital Clínico Universitario Virgen de la Arrixaca, Murcia, Spain;

14. Hospital Costa del Sol, Marbella, Spain;

15. Institut Català d’Oncologia;

16. Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain;

17. Hospital Puerta de Hierro, Madrid, Spain;

18. Hospital Son Espases, Palma, Spain;

19. Hospital Doctor Peset, Valencia, Spain;

20. Hospital de Galdakao, Vizcaya, Spain;

21. Instituto Murciano de Investigación Biosanitaria (IMIB), Hospital Universitario Morales Meseguer, Arrixaca, Spain;

22. UOS Diagnostica Molecolare Ematologica, Campus Bio-Medico University of Rome, Rome, Italy; and

23. Department of Immunology, Weizmann Institute of Science, Rehovot, Israel

Abstract

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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3