Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study

Autores
Bengió, Raquel M.; Riva, Maria E.; Moiraghi, Beatriz; Lanari, Emilio; Milone, Jorge; Ventriglia, Veronica; Bullorsky, Eduardo; de Tezanos Pinto, Miguel; Murro, Hector; Bianchini, Michele; Larripa, Irene Beatriz
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early.
Fil: Bengió, Raquel M.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Riva, Maria E.. Hospital San Mart́n; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Lanari, Emilio. Hospital Jose Ramon Vidal ; Gobierno de la Provincia de Corrientes;
Fil: Milone, Jorge. Hospital Italiano; Argentina
Fil: Ventriglia, Veronica. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; Argentina
Fil: de Tezanos Pinto, Miguel. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Murro, Hector. No especifíca;
Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
BCRABL
CML
IMATINIB
MUTATIONS
P-LOOP
RESISTANCE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/193358
Acceder
id CONICETDig_fa78eb34f94b61fcaf72194c8d5f3b41
oai_identifier_str oai:ri.conicet.gov.ar:11336/193358
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean studyBengió, Raquel M.Riva, Maria E.Moiraghi, BeatrizLanari, EmilioMilone, JorgeVentriglia, VeronicaBullorsky, Eduardode Tezanos Pinto, MiguelMurro, HectorBianchini, MicheleLarripa, Irene BeatrizBCRABLCMLIMATINIBMUTATIONSP-LOOPRESISTANCEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early.Fil: Bengió, Raquel M.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Riva, Maria E.. Hospital San Mart́n; ArgentinaFil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Lanari, Emilio. Hospital Jose Ramon Vidal ; Gobierno de la Provincia de Corrientes;Fil: Milone, Jorge. Hospital Italiano; ArgentinaFil: Ventriglia, Veronica. Hospital Nacional Profesor Alejandro Posadas; ArgentinaFil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; ArgentinaFil: de Tezanos Pinto, Miguel. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Murro, Hector. No especifíca;Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaTaylor & Francis Ltd2011-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/193358Bengió, Raquel M.; Riva, Maria E.; Moiraghi, Beatriz; Lanari, Emilio; Milone, Jorge; et al.; Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study; Taylor & Francis Ltd; Leukemia and Lymphoma; 52; 9; 9-2011; 1720-17261042-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/10428194.2011.578310?journalCode=ilal20info:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2011.578310info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:56:49Zoai:ri.conicet.gov.ar:11336/193358instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:56:49.803CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
title Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
spellingShingle Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
Bengió, Raquel M.
BCRABL
CML
IMATINIB
MUTATIONS
P-LOOP
RESISTANCE
title_short Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
title_full Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
title_fullStr Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
title_full_unstemmed Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
title_sort Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study
dc.creator.none.fl_str_mv Bengió, Raquel M.
Riva, Maria E.
Moiraghi, Beatriz
Lanari, Emilio
Milone, Jorge
Ventriglia, Veronica
Bullorsky, Eduardo
de Tezanos Pinto, Miguel
Murro, Hector
Bianchini, Michele
Larripa, Irene Beatriz
author Bengió, Raquel M.
author_facet Bengió, Raquel M.
Riva, Maria E.
Moiraghi, Beatriz
Lanari, Emilio
Milone, Jorge
Ventriglia, Veronica
Bullorsky, Eduardo
de Tezanos Pinto, Miguel
Murro, Hector
Bianchini, Michele
Larripa, Irene Beatriz
author_role author
author2 Riva, Maria E.
Moiraghi, Beatriz
Lanari, Emilio
Milone, Jorge
Ventriglia, Veronica
Bullorsky, Eduardo
de Tezanos Pinto, Miguel
Murro, Hector
Bianchini, Michele
Larripa, Irene Beatriz
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BCRABL
CML
IMATINIB
MUTATIONS
P-LOOP
RESISTANCE
topic BCRABL
CML
IMATINIB
MUTATIONS
P-LOOP
RESISTANCE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early.
Fil: Bengió, Raquel M.. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Riva, Maria E.. Hospital San Mart́n; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Lanari, Emilio. Hospital Jose Ramon Vidal ; Gobierno de la Provincia de Corrientes;
Fil: Milone, Jorge. Hospital Italiano; Argentina
Fil: Ventriglia, Veronica. Hospital Nacional Profesor Alejandro Posadas; Argentina
Fil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; Argentina
Fil: de Tezanos Pinto, Miguel. Academia Nacional de Medicina de Buenos Aires; Argentina
Fil: Murro, Hector. No especifíca;
Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description In imatinib-treated patients with chronic myeloid leukemia (CML), BCRABL mutations are the most common mechanism of resistance. Here we report the first multicenter Argentinean study investigating mutations in those patients with CML who fail or lose response to imatinib, with or without previous interferon treatment. Point mutations were detected in 36 of 154 patients by direct sequencing. In our series, the single most common mutations were G250E, E255K/V, and M351T. The presence of mutations correlated significantly with accelerated phase, lack of molecular response, and lower cytogenetic and hematological responses. While overall survival did not differ between patients with or without mutations, the probability of progression was higher in patients with mutations. Cases with non-P-loop mutations showed a significantly better overall survival from diagnosis. Multivariate analysis showed that the most significant variables related to the development of mutations were accelerated phase, duration of imatinib treatment, and time delay to starting imatinib. Our results demonstrated that mutation frequency increased with the progression of disease, and suggest that imatinib treatment should be started early.
publishDate 2011
dc.date.none.fl_str_mv 2011-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/193358
Bengió, Raquel M.; Riva, Maria E.; Moiraghi, Beatriz; Lanari, Emilio; Milone, Jorge; et al.; Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study; Taylor & Francis Ltd; Leukemia and Lymphoma; 52; 9; 9-2011; 1720-1726
1042-8194
CONICET Digital
CONICET
url http://hdl.handle.net/11336/193358
identifier_str_mv Bengió, Raquel M.; Riva, Maria E.; Moiraghi, Beatriz; Lanari, Emilio; Milone, Jorge; et al.; Clinical outcome of chronic myeloid leukemia imatinib-resistant patients: Do BCRABL kinase domain mutations affect patient survival? First multicenter Argentinean study; Taylor & Francis Ltd; Leukemia and Lymphoma; 52; 9; 9-2011; 1720-1726
1042-8194
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/10428194.2011.578310?journalCode=ilal20
info:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2011.578310
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Taylor & Francis Ltd
publisher.none.fl_str_mv Taylor & Francis Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269426457509888
score 13.13397

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