The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome

© 2021 Rodríguez-Caballero, Fuentes Herrero, Oliva Ariza, Criado, Alcoceba, Prieto, Pérez Caro, García-Montero, González Díaz, Forconi, Sarmento-Ribeiro, Almeida and Orfao.

Detalhes bibliográficos
Autores: Rodríguez-Caballero, Arancha, Fuentes-Herrero, Blanca, Oliva-Ariza, Guillermo, Criado, Ignacio, Alcoceba, Miguel, Prieto, Carlos, Pérez-Caro, M., García-Montero, Andrés, González, Marcos, Forconi, F., Sarmento-Ribeiro, Ana Bela, Almeida, Julia, Orfao, Alberto
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/262270
Acesso em linha:http://hdl.handle.net/10261/262270
Access Level:acceso abierto
Palavra-chave:Hydropathy index
Neutral HCDR3
Negatively charged HCDR3
Mutated CLL (M-CLL)
Disease progression
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spelling The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct OutcomeRodríguez-Caballero, AranchaFuentes-Herrero, BlancaOliva-Ariza, GuillermoCriado, IgnacioAlcoceba, MiguelPrieto, CarlosPérez-Caro, M.García-Montero, AndrésGonzález, MarcosForconi, F.Sarmento-Ribeiro, Ana BelaAlmeida, JuliaOrfao, AlbertoHydropathy indexNeutral HCDR3Negatively charged HCDR3Mutated CLL (M-CLL)Disease progression© 2021 Rodríguez-Caballero, Fuentes Herrero, Oliva Ariza, Criado, Alcoceba, Prieto, Pérez Caro, García-Montero, González Díaz, Forconi, Sarmento-Ribeiro, Almeida and Orfao.The HCDR3 sequences of the B-cell receptor (BCR) undergo constraints in length, amino acid use, and charge during maturation of B-cell precursors and after antigen encounter, leading to BCR and antibodies with high affinity to specific antigens. Chronic lymphocytic leukemia consists of an expansion of B-cells with a mixed immature and “antigen-experienced” phenotype, with either a mutated (M-CLL) or unmutated (U-CLL) tumor BCR, associated with distinct patient outcomes. Here, we investigated the hydropathy index of the BCR of 138 CLL patients and its association with the IGHV mutational status and patient outcome. Overall, two clearly distinct subgroups of M-CLL patients emerged, based on a neutral (mean hydropathy index of -0.1) vs. negatively charged BCR (mean hydropathy index of -1.1) with molecular features closer to those of B-cell precursors and peripheral/mature B-cells, respectively. Despite that M-CLL with neutral HCDR3 did not show traits associated with a mature B-cell repertoire, important differences in IGHV gene usage of tumor cells and patient outcome were observed in this subgroup of patients once compared to both U-CLL and M-CLL with negatively charged HCDR3 sequences. Compared to M-CLL with negatively charged HCDR3 sequences, M-CLL with neutral HCDR3 sequences showed predominance of men, more advanced stages of the disease, and a greater frequency of genetic alterations—e.g., del(17p)—together with a higher rate of disease progression and shorter time to therapy (TTT), independently of other prognostic factors. Our data suggest that the hydropathy index of the HCDR3 sequences of CLL cells allows the identification of a subgroup of M-CLL with intermediate prognostic features between U-CLL and the more favorable subgroup of M-CLL with a negatively charged BCR.This work was supported by the following grants: FS/37-2017, from the Fundación Memoria D. Samuel Solórzano, Universidad de Salamanca; FIS PI17/00399-FEDER, from the Fondo de Investigación Sanitaria of Instituto de Salud Carlos III, Madrid, Spain; 0639_IDIAL_NET_3_E, from cooperative network EPINTERREG V A España Portugal (POCTEP); and ECRIN-M3, Accelerator Award Full, Cancer Research UK, Fundación Cientıfíca de la Asociación Española Contra el Cáncer (AECC), Fondazione AIRC per la Ricerca sul Cancro. TFrontiers MediaFundación Memoria de D. Samuel Solorzano BarrusoUniversidad de SalamancaEuropean CommissionInstituto de Salud Carlos IIICancer Research UKAsociación Española Contra el CáncerAssociazione Italiana per la Ricerca sul CancroConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220212022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/262270reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.3389/fonc.2021.723722Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2622702026-05-22T06:33:51Z
dc.title.none.fl_str_mv The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
title The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
spellingShingle The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
Rodríguez-Caballero, Arancha
Hydropathy index
Neutral HCDR3
Negatively charged HCDR3
Mutated CLL (M-CLL)
Disease progression
title_short The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
title_full The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
title_fullStr The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
title_full_unstemmed The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
title_sort The Hydropathy Index of the HCDR3 Region of the B-Cell Receptor Identifies Two Subgroups of IGHV-Mutated Chronic Lymphocytic Leukemia Patients With Distinct Outcome
dc.creator.none.fl_str_mv Rodríguez-Caballero, Arancha
Fuentes-Herrero, Blanca
Oliva-Ariza, Guillermo
Criado, Ignacio
Alcoceba, Miguel
Prieto, Carlos
Pérez-Caro, M.
García-Montero, Andrés
González, Marcos
Forconi, F.
Sarmento-Ribeiro, Ana Bela
Almeida, Julia
Orfao, Alberto
author Rodríguez-Caballero, Arancha
author_facet Rodríguez-Caballero, Arancha
Fuentes-Herrero, Blanca
Oliva-Ariza, Guillermo
Criado, Ignacio
Alcoceba, Miguel
Prieto, Carlos
Pérez-Caro, M.
García-Montero, Andrés
González, Marcos
Forconi, F.
Sarmento-Ribeiro, Ana Bela
Almeida, Julia
Orfao, Alberto
author_role author
author2 Fuentes-Herrero, Blanca
Oliva-Ariza, Guillermo
Criado, Ignacio
Alcoceba, Miguel
Prieto, Carlos
Pérez-Caro, M.
García-Montero, Andrés
González, Marcos
Forconi, F.
Sarmento-Ribeiro, Ana Bela
Almeida, Julia
Orfao, Alberto
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Fundación Memoria de D. Samuel Solorzano Barruso
Universidad de Salamanca
European Commission
Instituto de Salud Carlos III
Cancer Research UK
Asociación Española Contra el Cáncer
Associazione Italiana per la Ricerca sul Cancro
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Hydropathy index
Neutral HCDR3
Negatively charged HCDR3
Mutated CLL (M-CLL)
Disease progression
topic Hydropathy index
Neutral HCDR3
Negatively charged HCDR3
Mutated CLL (M-CLL)
Disease progression
description © 2021 Rodríguez-Caballero, Fuentes Herrero, Oliva Ariza, Criado, Alcoceba, Prieto, Pérez Caro, García-Montero, González Díaz, Forconi, Sarmento-Ribeiro, Almeida and Orfao.
publishDate 2021
dc.date.none.fl_str_mv 2021
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/262270
url http://hdl.handle.net/10261/262270
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.3389/fonc.2021.723722
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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