A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics

BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and...

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Autores: Sánchez, Ricardo, Ribera, Jordi, Morgades, Mireia, Ayala, Rosa, Onecha, Esther, Ruiz Heredia, Yanira, Juárez Rufián, Alexandra, Nicolás, Rodrigo de, Sánchez Pina, José, Vives, Susana, Zamora, Lurdes, Mercadal, Santiago, Coll, Rosa, Cervera, Marta, Garcia, Olga, Ribera, Josep Maria, Martínez López, Joaquín
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2020
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/173078
Acesso em linha:https://hdl.handle.net/2445/173078
Access Level:acceso abierto
Palavra-chave:Leucèmia limfocítica crònica
Pronòstic mèdic
Chronic lymphocytic leukemia
Prognosis
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spelling A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristicsSánchez, RicardoRibera, JordiMorgades, MireiaAyala, RosaOnecha, EstherRuiz Heredia, YaniraJuárez Rufián, AlexandraNicolás, Rodrigo deSánchez Pina, JoséVives, SusanaZamora, LurdesMercadal, SantiagoColl, RosaCervera, MartaGarcia, OlgaRibera, Josep MariaMartínez López, JoaquínLeucèmia limfocítica crònicaPronòstic mèdicChronic lymphocytic leukemiaPrognosisBCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P <= 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.Nature Publishing Group2021202120202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion11 p.application/pdfapplication/pdfhttps://hdl.handle.net/2445/173078Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41408-020-0308-3Blood Cancer Journal, 2020, vol. 10, num. 4https://doi.org/10.1038/s41408-020-0308-3cc by (c) Sánchez et al., 2020http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1730782026-05-29T05:05:01Z
dc.title.none.fl_str_mv A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
title A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
spellingShingle A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
Sánchez, Ricardo
Leucèmia limfocítica crònica
Pronòstic mèdic
Chronic lymphocytic leukemia
Prognosis
title_short A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
title_full A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
title_fullStr A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
title_full_unstemmed A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
title_sort A novel targeted RNA-Seq panel identifies a subset of adult patients with acute lymphoblastic leukemia with BCR-ABL1-like characteristics
dc.creator.none.fl_str_mv Sánchez, Ricardo
Ribera, Jordi
Morgades, Mireia
Ayala, Rosa
Onecha, Esther
Ruiz Heredia, Yanira
Juárez Rufián, Alexandra
Nicolás, Rodrigo de
Sánchez Pina, José
Vives, Susana
Zamora, Lurdes
Mercadal, Santiago
Coll, Rosa
Cervera, Marta
Garcia, Olga
Ribera, Josep Maria
Martínez López, Joaquín
author Sánchez, Ricardo
author_facet Sánchez, Ricardo
Ribera, Jordi
Morgades, Mireia
Ayala, Rosa
Onecha, Esther
Ruiz Heredia, Yanira
Juárez Rufián, Alexandra
Nicolás, Rodrigo de
Sánchez Pina, José
Vives, Susana
Zamora, Lurdes
Mercadal, Santiago
Coll, Rosa
Cervera, Marta
Garcia, Olga
Ribera, Josep Maria
Martínez López, Joaquín
author_role author
author2 Ribera, Jordi
Morgades, Mireia
Ayala, Rosa
Onecha, Esther
Ruiz Heredia, Yanira
Juárez Rufián, Alexandra
Nicolás, Rodrigo de
Sánchez Pina, José
Vives, Susana
Zamora, Lurdes
Mercadal, Santiago
Coll, Rosa
Cervera, Marta
Garcia, Olga
Ribera, Josep Maria
Martínez López, Joaquín
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Leucèmia limfocítica crònica
Pronòstic mèdic
Chronic lymphocytic leukemia
Prognosis
topic Leucèmia limfocítica crònica
Pronòstic mèdic
Chronic lymphocytic leukemia
Prognosis
description BCR-ABL1-like B-cell precursor acute lymphoblastic leukemia (BCP-ALL) remains poorly characterized in adults. We sought to establish the frequency and outcome of adolescent and adult BCR-ABL1-like ALL using a novel RNA-Seq signature in a series of patients with BCP-ALL. To this end, we developed and tested an RNA-Seq custom panel of 42 genes related to a BCR-ABL1-like signature in a cohort of 100 patients with BCP-ALL and treated with risk-adapted ALL trials. Mutations related to BCR-ABL1-like ALL were studied in a panel of 33 genes by next-generation sequencing (NGS). Also, CRLF2 overexpression and IKZF1/CDKN2A/B deletions were analyzed. Twenty out of 79 patients (12-84 years) were classified as BCR-ABL1-like (25%) based on heatmap clustering, with significant overexpression of ENAM, IGJ, and CRLF2 (P <= 0.001). The BCR-ABL1-like subgroup accounted for 29% of 15-60-year-old patients, with the following molecular characteristics: CRLF2 overexpression (75% of cases), IKZF1 deletions (64%), CDKN2A/B deletions (57%), and JAK2 mutations (57%). Among patients with postinduction negative minimal residual disease, those with the BCR-ABL1-like ALL signature had a higher rate of relapse and lower complete response duration than non-BCR-ABL1-like patients (P = 0.007). Thus, we have identified a new molecular signature of BCR-ABL1-like ALL that correlates with adverse prognosis in adult patients with ALL.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/173078
url https://hdl.handle.net/2445/173078
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41408-020-0308-3
Blood Cancer Journal, 2020, vol. 10, num. 4
https://doi.org/10.1038/s41408-020-0308-3
dc.rights.none.fl_str_mv cc by (c) Sánchez et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Sánchez et al., 2020
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 11 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.81155

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