Evidence map›Paper›PMID 25388955›Full record

ArticleLeukemia2015

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential.

T Paíno, B Paiva, J M Sayagués, I Mota, T Carvalheiro, L A Corchete, I Aires-Mejía, J J Pérez, M L Sanchez, P Barcena and 15 more

Abstract read
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In one paragraph

Article in Leukemia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 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.

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

48 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

25 authors.

T Paíno1] Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain [2] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
B PaivaClínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.
J M Sayagués1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Servicio General de Citometría y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
I MotaServicio General de Citometría y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
T CarvalheiroCentro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal.
L A Corchete1] Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain [2] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
I Aires-MejíaHospital Universitario de Salamanca, Salamanca, Spain.
J J PérezHospital Universitario de Salamanca, Salamanca, Spain.
M L SanchezServicio General de Citometría y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
P BarcenaServicio General de Citometría y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
E M Ocio1] Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain [2] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [3] Hospital Universitario de Salamanca, Salamanca, Spain.
L San-Segundo1] Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer/Consejo Superior de Investigaciones Científicas-Universidad de Salamanca (IBMCC, USAL-CSIC), Salamanca, Spain [2] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.
M E Sarasquete1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Hospital Universitario de Salamanca, Salamanca, Spain.
R García-Sanz1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Hospital Universitario de Salamanca, Salamanca, Spain.
M-B Vidriales1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Hospital Universitario de Salamanca, Salamanca, Spain.
A OriolHospital Germans Trias i Pujol, Badalona, Spain.
M-T HernándezHospital Universitario de Canarias, Santa Cruz de Tenerife, Spain.
M-A EchevesteHospital de Donostia, San Sebastian, Spain.
A PaivaCentro do Sangue e da Transplantação de Coimbra, Instituto Português do Sangue e da Transplantação, Coimbra, Portugal.
J BladeHospital Clínic, IDIBAPS, Salamanca, Spain.
J-J LahuertaHospital 12 de Octubre, Madrid, Spain.
A Orfao1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Servicio General de Citometría y Departamento de Medicina, Universidad de Salamanca, Salamanca, Spain.
M-V Mateos1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Hospital Universitario de Salamanca, Salamanca, Spain.
N C Gutiérrez1] Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain [2] Hospital Universitario de Salamanca, Salamanca, Spain.
J F San-MiguelClínica Universidad de Navarra, Centro de Investigaciones Médicas Aplicadas (CIMA), Pamplona, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.

Indexed as

Cell SeparationCoculture TechniquesDisease ProgressionDrug Resistance, NeoplasmFlow CytometryHumansImmunophenotypingIn Situ Hybridization, FluorescenceMultiple MyelomaPhenotypePlasma CellsPrincipal Component AnalysisPrognosisStromal Cells

Identifiers

PMID25388955

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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.