Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia

B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with progno...

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Autores: Ramos-Muntada, Mireia, Trincado, Juan L.., Blanco, J. (Joan), Bueno, Clara, Rodríguez Cortez, Virginia Carolina, Bataller Torralba, Alex, Lopez Millan, Maria Belén, Schwab, Claire, Ortega Blanco, Margarita, Velasco, Pablo, Blanco, Maria L., Nomdedéu Guinot, Josep Francesc, Ramírez-Orellana, Manuel, Minguela, Alfredo, Fuster, José Luis, Cuatrecasas, Esther, Camós Guijosa, Mireia, Ballerini, Paola, Escherich, Gabriele, Boer, Judith M., Den Boer, Monique L., Hernández-Rivas, Jesús María, Calasanz, María José, Cazzaniga, Giovanni, Harrison, Christine J., Menéndez, Pablo, Molina, Òscar
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/218548
Acceso en línea:https://hdl.handle.net/2445/218548
Access Level:acceso abierto
Palabra clave:Anomalies cromosòmiques
Infants
Factors de risc en les malalties
Leucèmia
Chromosome abnormalities
Children
Risk factors in diseases
Leukemia
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spelling Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemiaRamos-Muntada, MireiaTrincado, Juan L..Blanco, J. (Joan)Bueno, ClaraRodríguez Cortez, Virginia CarolinaBataller Torralba, AlexLopez Millan, Maria BelénSchwab, ClaireOrtega Blanco, MargaritaVelasco, PabloBlanco, Maria L.Nomdedéu Guinot, Josep FrancescRamírez-Orellana, ManuelMinguela, AlfredoFuster, José LuisCuatrecasas, EstherCamós Guijosa, MireiaBallerini, PaolaEscherich, GabrieleBoer, Judith M.Den Boer, Monique L.Hernández-Rivas, Jesús MaríaCalasanz, María JoséCazzaniga, GiovanniHarrison, Christine J.Menéndez, PabloMolina, ÒscarAnomalies cromosòmiquesInfantsFactors de risc en les malaltiesLeucèmiaChromosome abnormalitiesChildrenRisk factors in diseasesLeukemiaB-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-B-ALL patients.Elsevier2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/218548Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1002/1878-0261.13276Molecular Oncology, 2022, vol. 16, num.16, p. 2899-2919https://doi.org/10.1002/1878-0261.13276cc-by (c) Ramos-Muntada, M. et al., 2022http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2185482026-05-27T06:46:51Z
dc.title.none.fl_str_mv Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
title Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
spellingShingle Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
Ramos-Muntada, Mireia
Anomalies cromosòmiques
Infants
Factors de risc en les malalties
Leucèmia
Chromosome abnormalities
Children
Risk factors in diseases
Leukemia
title_short Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
title_full Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
title_fullStr Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
title_full_unstemmed Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
title_sort Clonal heterogeneity and rates of specific chromosome gains are risk predictors in childhood high-hyperdiploid B-cell acute lymphoblastic leukemia
dc.creator.none.fl_str_mv Ramos-Muntada, Mireia
Trincado, Juan L..
Blanco, J. (Joan)
Bueno, Clara
Rodríguez Cortez, Virginia Carolina
Bataller Torralba, Alex
Lopez Millan, Maria Belén
Schwab, Claire
Ortega Blanco, Margarita
Velasco, Pablo
Blanco, Maria L.
Nomdedéu Guinot, Josep Francesc
Ramírez-Orellana, Manuel
Minguela, Alfredo
Fuster, José Luis
Cuatrecasas, Esther
Camós Guijosa, Mireia
Ballerini, Paola
Escherich, Gabriele
Boer, Judith M.
Den Boer, Monique L.
Hernández-Rivas, Jesús María
Calasanz, María José
Cazzaniga, Giovanni
Harrison, Christine J.
Menéndez, Pablo
Molina, Òscar
author Ramos-Muntada, Mireia
author_facet Ramos-Muntada, Mireia
Trincado, Juan L..
Blanco, J. (Joan)
Bueno, Clara
Rodríguez Cortez, Virginia Carolina
Bataller Torralba, Alex
Lopez Millan, Maria Belén
Schwab, Claire
Ortega Blanco, Margarita
Velasco, Pablo
Blanco, Maria L.
Nomdedéu Guinot, Josep Francesc
Ramírez-Orellana, Manuel
Minguela, Alfredo
Fuster, José Luis
Cuatrecasas, Esther
Camós Guijosa, Mireia
Ballerini, Paola
Escherich, Gabriele
Boer, Judith M.
Den Boer, Monique L.
Hernández-Rivas, Jesús María
Calasanz, María José
Cazzaniga, Giovanni
Harrison, Christine J.
Menéndez, Pablo
Molina, Òscar
author_role author
author2 Trincado, Juan L..
Blanco, J. (Joan)
Bueno, Clara
Rodríguez Cortez, Virginia Carolina
Bataller Torralba, Alex
Lopez Millan, Maria Belén
Schwab, Claire
Ortega Blanco, Margarita
Velasco, Pablo
Blanco, Maria L.
Nomdedéu Guinot, Josep Francesc
Ramírez-Orellana, Manuel
Minguela, Alfredo
Fuster, José Luis
Cuatrecasas, Esther
Camós Guijosa, Mireia
Ballerini, Paola
Escherich, Gabriele
Boer, Judith M.
Den Boer, Monique L.
Hernández-Rivas, Jesús María
Calasanz, María José
Cazzaniga, Giovanni
Harrison, Christine J.
Menéndez, Pablo
Molina, Òscar
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Anomalies cromosòmiques
Infants
Factors de risc en les malalties
Leucèmia
Chromosome abnormalities
Children
Risk factors in diseases
Leukemia
topic Anomalies cromosòmiques
Infants
Factors de risc en les malalties
Leucèmia
Chromosome abnormalities
Children
Risk factors in diseases
Leukemia
description B-cell acute lymphoblastic leukemia (B-ALL) is the commonest childhood cancer. High hyperdiploidy (HHD) identifies the most frequent cytogenetic subgroup in childhood B-ALL. Although hyperdiploidy represents an important prognostic factor in childhood B-ALL, the specific chromosome gains with prognostic value in HHD-B-ALL remain controversial, and the current knowledge about the hierarchy of chromosome gains, clonal heterogeneity and chromosomal instability in HHD-B-ALL remains very limited. We applied automated sequential-iFISH coupled with single-cell computational modeling to identify the specific chromosomal gains of the eight typically gained chromosomes in a large cohort of 72 primary diagnostic (DX, n = 62) and matched relapse (REL, n = 10) samples from HHD-B-ALL patients with either favorable or unfavorable clinical outcome in order to characterize the clonal heterogeneity, specific chromosome gains and clonal evolution. Our data show a high degree of clonal heterogeneity and a hierarchical order of chromosome gains in DX samples of HHD-B-ALL. The rates of specific chromosome gains and clonal heterogeneity found in DX samples differ between HHD-B-ALL patients with favorable or unfavorable clinical outcome. In fact, our comprehensive analyses at DX using a computationally defined risk predictor revealed low levels of trisomies +18+10 and low levels of clonal heterogeneity as robust relapse risk factors in minimal residual disease (MRD)-negative childhood HHD-B-ALL patients: relapse-free survival beyond 5 years: 22.1% versus 87.9%, P < 0.0001 and 33.3% versus 80%, P < 0.0001, respectively. Moreover, longitudinal analysis of matched DX-REL HHD-B-ALL samples revealed distinct patterns of clonal evolution at relapse. Our study offers a reliable prognostic sub-stratification of pediatric MRD-negative HHD-B-ALL patients.
publishDate 2022
dc.date.none.fl_str_mv 2022
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/2445/218548
url https://hdl.handle.net/2445/218548
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/10.1002/1878-0261.13276
Molecular Oncology, 2022, vol. 16, num.16, p. 2899-2919
https://doi.org/10.1002/1878-0261.13276
dc.rights.none.fl_str_mv cc-by (c) Ramos-Muntada, M. et al., 2022
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Ramos-Muntada, M. et al., 2022
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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