Evidence map›Paper›PMID 32350373›Full record

ArticleLeukemia2021

Upregulation of CD38 expression on multiple myeloma cells by novel HDAC6 inhibitors is a class effect and augments the efficacy of daratumumab.

Estefanía García-Guerrero, Ralph Götz, Sören Doose, Markus Sauer, Alfonso Rodríguez-Gil, Thomas Nerreter, K Martin Kortüm, José A Pérez-Simón, Hermann Einsele, Michael Hudecek and 1 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
6.4field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 71 citations in OpenAlex.

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  5. PET Imaging of CD38 and IND enabling studies of [Molecular imaging and biology · 2026
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Estefanía García-GuerreroInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Ralph GötzDepartment of Biotechnology and Biophysics, Biocenter, and RVZ for Integrative and Translational BioImaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Sören DooseDepartment of Biotechnology and Biophysics, Biocenter, and RVZ for Integrative and Translational BioImaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Markus SauerDepartment of Biotechnology and Biophysics, Biocenter, and RVZ for Integrative and Translational BioImaging, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
Alfonso Rodríguez-GilInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Thomas NerreterMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.ORCID http://orcid.org/0000-0002-0493-1369
K Martin KortümMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
José A Pérez-SimónInstituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Hermann EinseleMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Michael HudecekMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany.
Sophia DanhofMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany. Danhof_S@ukw.de.ORCID http://orcid.org/0000-0003-1316-0241
Universitätsklinikum Würzburg · DEInstituto de Biomedicina de Sevilla · ESUniversity of Würzburg · DEUniversitäts-Kinderklinik Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple myeloma (MM) is incurable, so there is a significant unmet need for effective therapy for patients with relapsed or refractory disease. This situation has not changed despite the recent approval of the anti-CD38 antibody daratumumab, one of the most potent agents in MM treatment. The efficiency of daratumumab might be improved by combining it with synergistic anti-MM agents. We therefore investigated the potential of the histone deacetylase (HDAC) inhibitor ricolinostat to up-regulate CD38 on MM cells, thereby enhancing the performance of CD38-specific therapies. Using quantitative reverse transcription polymerase chain reaction and flow cytometry, we observed that ricolinostat significantly increases CD38 RNA levels and CD38 surface expression on MM cells. Super-resolution microscopy imaging of MM cells by direct stochastic optical reconstruction microscopy confirmed this rise with molecular resolution and revealed homogeneous distribution of CD38 molecules on the cell membrane. Particularly important is that combining ricolinostat with daratumumab induced enhanced lysis of MM cells. We also evaluated next-generation HDAC6 inhibitors (ACY-241, WT-161) and observed similar increase of CD38 levels suggesting that the upregulation of CD38 expression on MM cells by HDAC6 inhibitors is a class effect. This proof-of-concept illustrates the potential benefit of combining HDAC6 inhibitors and CD38-directed immunotherapy for MM treatment.

Indexed as

ADP-ribosyl Cyclase 1Antibodies, MonoclonalAntibody-Dependent Cell CytotoxicityAntineoplastic AgentsCell Line, TumorDrug SynergismGene Expression Regulation, NeoplasticHistone Deacetylase 6Histone Deacetylase InhibitorsHumansHydroxamic AcidsImmunophenotypingMembrane GlycoproteinsModels, BiologicalMultiple MyelomaPyrimidinesADP-ribosyl Cyclase 1Antibodies, MonoclonalAntineoplastic AgentsCD38 protein, humandaratumumabHDAC6 protein, humanHistone Deacetylase 6Histone Deacetylase InhibitorsHydroxamic AcidsMembrane GlycoproteinsPyrimidinesricolinostat

Identifiers

PMID32350373
PMCPMC8318885
OpenAlexW3023904386

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.