Evidence map›Paper›PMID 35610346›Full record

ArticleLeukemia2022

An N-glycosylation hotspot in immunoglobulin κ light chains is associated with AL amyloidosis.

Alice Nevone, Maria Girelli, Silvia Mangiacavalli, Bruno Paiva, Paolo Milani, Pasquale Cascino, Maggie Piscitelli, Valentina Speranzini, Claudio Salvatore Cartia, Pietro Benvenuti and 18 more

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In one paragraph

Article in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 29 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

28 authors at 6 institutions in 2 countries.

Alice NevoneDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Maria GirelliDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Silvia MangiacavalliDivision of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Bruno PaivaClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CIBER-ONC number CB16/12/00369, Instituto de Investigacion Sanitaria de Navarra (IDISNA), Navarra, Spain.ORCID 0000-0003-1977-3815
Paolo MilaniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0002-2268-9422
Pasquale CascinoDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Maggie PiscitelliDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Valentina SperanziniDipartimento di Bioscienze, Università Degli Studi di Milano, Milan, Italy.ORCID 0000-0002-7219-3097
Claudio Salvatore CartiaDivision of Hematology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.ORCID 0000-0002-0389-4164
Pietro BenvenutiAmyloidosis Research and Treatment Center, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Ibai GoicoecheaClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), CIBER-ONC number CB16/12/00369, Instituto de Investigacion Sanitaria de Navarra (IDISNA), Navarra, Spain.ORCID 0000-0002-5329-2225
Francesca FazioHematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Marco BassetDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0003-3829-0499
Andrea FoliDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Martina NanciDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Giulia MazziniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Serena CaminitoDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Melania Antonietta SestaDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Simona CasariniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0003-4730-7467
Paola RognoniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0001-6350-1919
Francesca LavatelliDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.
Maria Teresa PetrucciHematology, Department of Translational and Precision Medicine, Azienda Ospedaliera Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Pier Paolo OlimpieriDepartment of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.
Stefano RicagnoDipartimento di Bioscienze, Università Degli Studi di Milano, Milan, Italy.
Luca ArcainiDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0002-9504-991X
Giampaolo MerliniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy.ORCID 0000-0001-7680-3254
Giovanni PalladiniDepartment of Molecular Medicine, University of Pavia, Pavia, Italy. giovanni.palladini@unipv.it.ORCID 0000-0001-5994-5138
Mario NuvoloneDepartment of Molecular Medicine, University of Pavia, Pavia, Italy. mario.nuvolone@unipv.it.ORCID 0000-0001-8334-1684
University of Pavia · ITPoliclinico San Matteo Fondazione · ITNavarre Institute of Health Research · ESPoliclinico Umberto I · ITUniversity of Milan · ITSapienza University of Rome · IT

Funding

Cancer Research UK C355/A26819
6 · The paper itself

Abstract

Immunoglobulin light chain (AL) amyloidosis is caused by a small, minimally proliferating B-cell/plasma-cell clone secreting a patient-unique, aggregation-prone, toxic light chain (LC). The pathogenicity of LCs is encrypted in their sequence, yet molecular determinants of amyloidogenesis are poorly understood. Higher rates of N-glycosylation among clonal κ LCs from patients with AL amyloidosis compared to other monoclonal gammopathies indicate that this post-translational modification is associated with a higher risk of developing AL amyloidosis. Here, we exploited LC sequence information from previously published amyloidogenic and control clonal LCs and from a series of 220 patients with AL amyloidosis or multiple myeloma followed at our Institutions to define sequence and spatial features of N-glycosylation, combining bioinformatics, biochemical, proteomics, structural and genetic analyses. We found peculiar sequence and spatial pattern of N-glycosylation in amyloidogenic κ LCs, with most of the N-glycosylation sites laying in the framework region 3, particularly within the E strand, and consisting mainly of the NFT sequon, setting them apart with respect to non-amyloidogenic clonal LCs. Our data further support a potential role of N-glycosylation in determining the pathogenic behavior of a subset of amyloidogenic LCs and may help refine current N-glycosylation-based prognostic assessments for patients with monoclonal gammopathies.

Indexed as

AmyloidosisImmunoglobulin Light-chain AmyloidosisMultiple MyelomaGlycosylationHumansImmunoglobulin kappa-ChainsImmunoglobulin Light ChainsImmunoglobulin kappa-ChainsImmunoglobulin Light Chains

Identifiers

PMID35610346
OpenAlexW4281394609

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.