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http://hdl.handle.net/10261/296519
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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Bueno, Clara | - |
dc.contributor.author | Barrera, Susana | - |
dc.contributor.author | Bataller, Alex | - |
dc.contributor.author | Ortiz-Maldonado, Valentín | - |
dc.contributor.author | Elliot, Natalina | - |
dc.contributor.author | O’Byrne, Sorcha | - |
dc.contributor.author | Wang, Guanlin | - |
dc.contributor.author | Rovira, Montserrat | - |
dc.contributor.author | Gutierrez-Aguera, Francisco | - |
dc.contributor.author | Trincado, Juan L. | - |
dc.contributor.author | González-González, María | - |
dc.contributor.author | Morgades, Mireia | - |
dc.contributor.author | Sorigué, Marc | - |
dc.contributor.author | Bárcena, Paloma | - |
dc.contributor.author | Zanetti, Samanta Romina | - |
dc.contributor.author | Torrebadell, Montse | - |
dc.contributor.author | Vega-García, Nerea | - |
dc.contributor.author | Rives, Susana | - |
dc.contributor.author | Mallo, Mar | - |
dc.contributor.author | Solé, Francesc | - |
dc.contributor.author | Mead, Adam J. | - |
dc.contributor.author | Roberts, Irene | - |
dc.contributor.author | Thongjuea, Supat | - |
dc.contributor.author | Psaila, Bethan | - |
dc.contributor.author | Juan, Manel | - |
dc.contributor.author | Delgado, Julio | - |
dc.contributor.author | Urbano-Ispizúa, Álvaro | - |
dc.contributor.author | Ribera, Josep-Maria | - |
dc.contributor.author | Orfao, Alberto | - |
dc.contributor.author | Roy, Anindita | - |
dc.contributor.author | Menéndez, Pablo | - |
dc.date.accessioned | 2023-03-02T14:30:03Z | - |
dc.date.available | 2023-03-02T14:30:03Z | - |
dc.date.issued | 2022-07-07 | - |
dc.identifier | doi: 10.1182/blood.2021014840 | - |
dc.identifier | issn: 0006-4971 | - |
dc.identifier | e-issn: 1528-0020 | - |
dc.identifier.citation | Blood 140(1): 38-44 (2022) | - |
dc.identifier.uri | http://hdl.handle.net/10261/296519 | - |
dc.description.abstract | CD19-directed immunotherapies have revolutionized the treatment of advanced B-cell acute lymphoblastic leukemia (B-ALL). Despite initial impressive rates of complete remission (CR) many patients ultimately relapse. Patients with B-ALL successfully treated with CD19-directed T cells eventually relapse, which, coupled with the early onset of CD22 expression during B-cell development, suggests that preexisting CD34+CD22+CD19− (pre)-leukemic cells represent an “early progenitor origin-related” mechanism underlying phenotypic escape to CD19-directed immunotherapies. We demonstrate that CD22 expression precedes CD19 expression during B-cell development. CD34+CD19−CD22+ cells are found in diagnostic and relapsed bone marrow samples of ∼70% of patients with B-ALL, and their frequency increases twofold in patients with B-ALL in CR after CD19 CAR T-cell therapy. The median of CD34+CD19−CD22+ cells before treatment was threefold higher in patients in whom B-ALL relapsed after CD19-directed immunotherapy (median follow-up, 24 months). Fluorescence in situ hybridization analysis in flow-sorted cell populations and xenograft modeling revealed that CD34+CD19−CD22+ cells harbor the genetic abnormalities present at diagnosis and initiate leukemogenesis in vivo. Our data suggest that preleukemic CD34+CD19−CD22+ progenitors underlie phenotypic escape after CD19-directed immunotherapies and reinforce ongoing clinical studies aimed at CD19/CD22 dual targeting as a strategy for reducing CD19− relapses. The implementation of CD34/CD19/CD22 immunophenotyping in clinical laboratories for initial diagnosis and subsequent monitoring of patients with B-ALL during CD19-targeted therapy is encouraged. | - |
dc.description.sponsorship | The work in P.M. and C.B.’s Laboratory was supported by the European Research Council (CoG-2014-646903, PoC-2018-811220) and the Spanish Ministry of Economy and Competitiveness (SAF2016-80481R, PID2019-108160RB-I00) (P.M.); the ISCIII (ISCIII/FEDER, PI17/01028 and PI20/00822), the Spanish Association against Cancer (AECC), and the FERO Foundation (C.B.). P.M. and J.M.R. acknowledge the support of ISCIII-RICORS within the Next Generation EU program (Plan de Recuperación, Transformación y Resiliencia). N.E. is supported by Cancer Research UK and a Children and Young People’s Cancer Innovation Award (DRCPGM\100058). A.R. is supported by a Wellcome Trust Clinical Research Career Development Fellowship (216632/Z/19/Z). A.O. was supported by ISCIII (PI19/011183). F.S. was supported by AGAUR/Generalitat de Catalunya (SGR288). The single-cell transcriptomic analysis was supported by MRC Discovery award MRCDA 0816-11 and the MRC WIMM Single Cell Facility and MRC-funded Oxford Consortium for Single-Cell Biology (MR/M00919X/1) provided assistance. | - |
dc.format | application/pdf | - |
dc.language | eng | - |
dc.publisher | American Society of Hematology | - |
dc.relation | info:eu-repo/grantAgreement/MINECO//SAF2016-80481R | - |
dc.relation | info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-108160RB-I00/ES/TIM3, UNA NUEVA Y PROMETEDORA DIANA INMUNOTERAPEUTICA EN LEUCEMIA LINFOBLASTICA AGUDA B DE NOVO Y EN RECAIDA/ | - |
dc.relation.isversionof | Publisher's version | - |
dc.rights | openAccess | - |
dc.subject | Brief Reports | - |
dc.subject | Free Research Articles | - |
dc.subject | Immunobiology and Immunotherapy | - |
dc.subject | Lymphoid Neoplasia | - |
dc.title | CD34+CD19−CD22+ B-cell progenitors may underlie phenotypic escape in patients treated with CD19-directed therapies | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1182/blood.2021014840 | es_ES |
dc.description.peerreviewed | Peer reviewed | - |
dc.relation.publisherversion | http://dx.doi.org/10.1182/blood.2021014840 | - |
dc.date.updated | 2023-03-02T14:30:03Z | - |
dc.rights.license | https://creativecommons.org/licenses/by-nc-nd/4.0/ | - |
dc.contributor.funder | European Research Council | - |
dc.contributor.funder | European Commission | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | Ministerio de Ciencia, Innovación y Universidades (España) | - |
dc.contributor.funder | Agencia Estatal de Investigación (España) | - |
dc.contributor.funder | Instituto de Salud Carlos III | - |
dc.contributor.funder | Cancer Research UK | - |
dc.contributor.funder | Wellcome Trust | - |
dc.contributor.funder | Generalitat de Catalunya | - |
dc.contributor.funder | University of Oxford | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000289 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000780 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000781 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100002809 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000769 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/100004440 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100011033 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.grantfulltext | open | - |
item.fulltext | With Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.cerifentitytype | Publications | - |
item.openairetype | artículo | - |
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CD34_Bueno_PV_Art2022.pdf | 4,49 MB | Adobe PDF | Visualizar/Abrir |
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