Evidence map›Paper›PMID 27479184›Full record

ArticleLeukemia2017

Differentiation stage of myeloma plasma cells: biological and clinical significance.

B Paiva, N Puig, M T Cedena, B G de Jong, Y Ruiz, I Rapado, J Martinez-Lopez, L Cordon, D Alignani, J A Delgado and 21 more

Registry-linked trialAbstract read
In one paragraph

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06109233 (A Perspective Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment), which is not on this map. Cited by 69 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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.

NCT06109233 unknown statusnot on this mapstarted 2022, after this paper: background citation

A Perspective Study of the MRD-tailored Therapy in Patients With Newly Diagnosed Multiple Myeloma With Persistent Minimal Residual Disease After Initial Treatment

TypeobservationalSponsorFengYan JinRan2022 to 2026Enrolled80ConditionsMultiple Myeloma, Minimal Residual Disease
3 · Its place in the literature

Who cites it

69 citing papers in PubMed, 2 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. Article
  8. Article
  9. Article
  10. 2025 Update of Cellular Immunotherapy for Plasma Cell Disorders.Turkish journal of haematology : official journal of Turkish Society of Haematology · 2026
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Are we there yet? CAR-T therapy in multiple myeloma.British journal of haematology · 2024
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. Article

9 more citing papers are in PubMed but not listed here.

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

31 authors.

B PaivaClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
N PuigHospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain.
M T CedenaHospital 12 de Octubre, Madrid, Spain.
B G de JongDepartment of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
Y RuizHospital 12 de Octubre, Madrid, Spain.
I RapadoHospital 12 de Octubre, Madrid, Spain.
J Martinez-LopezHospital 12 de Octubre, Madrid, Spain.
L CordonHospital Universitario y Politécnico La Fe, Valencia, Spain.
D AlignaniClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
J A DelgadoClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
M C van ZelmDepartment of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
J J M Van DongenDepartment of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
M PascualClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
X AgirreClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
F ProsperClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.
J I Martín-SuberoUnidad de Hematopatología, Servicio de Anatomía Patológica, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
M-B VidrialesHospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain.
N C GutierrezHospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain.
M T HernandezHospital Universitario de Canarias, Tenerife, Spain.
A OriolInstitut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias I Pujol, Badalona, Spain.
M A EchevesteHospital de Donostia, San Sebastian, Spain.
Y GonzalezHospital Universitario Josep Trueta, Girona, Spain.
S K JohnsonMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
J EpsteinMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
B BarlogieMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
G J MorganMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
A OrfaoServicio General de Citometría, Centro de Investigación del Cancer (IBMCC-USAL, CSIC), IBSAL and Department of Medicine, Universidad de Salamanca, Salamanca, Spain.
J BladeHospital Clínic, IDIBAPS, Barcelona, Spain.
M V MateosHospital Universitario de Salamanca, Instituto de Investigacion Biomedica de Salamanca (IBSAL), Centro de Investigación del Cancer (IBMCC-USAL, CSIC), Salamanca, Spain.
J J LahuertaHospital 12 de Octubre, Madrid, Spain.
J F San-MiguelClinica Universidad de Navarra, Centro de Investigacion Medica Aplicada (CIMA), IDISNA, Pamplona, Spain.

Funding

European Research Council 680200
6 · The paper itself

Abstract

The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19-CD81-) clones, 38% intermediate-differentiated (CD19-CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P=0.005) and overall survival (HR: 2.1; P=0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n=40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.

Indexed as

AdultAntigens, CDBiomarkersBone MarrowBone Marrow CellsCase-Control StudiesCell CycleDNA MethylationFemaleGene Expression ProfilingGenetic HeterogeneityHigh-Throughput Nucleotide SequencingHumansImmunophenotypingIn Situ Hybridization, FluorescenceMaleAntigens, CDBiomarkers

Identifiers

PMID27479184
PMCPMC5439510

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Registered trials

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.