dc.creator | García-Guerrero, Estefanía | es |
dc.creator | Götz, Ralph | es |
dc.creator | Doose, Sören | es |
dc.creator | Sauer, Markus | es |
dc.creator | Rodríguez Gil, Alfonso | es |
dc.creator | Pérez Simón, José Antonio | es |
dc.creator | Danhof, Sophia | es |
dc.date.accessioned | 2022-09-28T16:24:34Z | |
dc.date.available | 2022-09-28T16:24:34Z | |
dc.date.issued | 2021 | |
dc.identifier.citation | García-Guerrero, E., Götz, R., Doose, S., Sauer, M., Rodríguez Gil, A., Pérez-Simón, J.A. y Danhof, S. (2021). Upregulation of CD38 expression on multiple myeloma cells by novel HDAC6 inhibitors is a class effect and augments the efficacy of daratumumab. Leukemia, 35 (1), 201-214. | |
dc.identifier.issn | 0887-6924 | es |
dc.identifier.issn | 1476-5551 | es |
dc.identifier.uri | https://hdl.handle.net/11441/137450 | |
dc.description.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 treatmen | es |
dc.format | application/pdf | es |
dc.format.extent | 14 p. | es |
dc.language.iso | eng | es |
dc.publisher | Nature Publishing Group | es |
dc.relation.ispartof | Leukemia, 35 (1), 201-214. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Multiple myeloma | es |
dc.subject | CD38 expression | es |
dc.subject | HDAC6 inhibitors | es |
dc.subject | Daratumumab | es |
dc.title | Upregulation of CD38 expression on multiple myeloma cells by novel HDAC6 inhibitors is a class effect and augments the efficacy of daratumumab | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología Médica y Biofísica | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Medicina | es |
dc.relation.publisherversion | http://doi.org/10.1038/s41375-020-0840-y | es |
dc.identifier.doi | 10.1038/s41375-020-0840-y | es |
dc.journaltitle | Leukemia | es |
dc.publication.volumen | 35 | es |
dc.publication.issue | 1 | es |
dc.publication.initialPage | 201 | es |
dc.publication.endPage | 214 | es |