Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients

Autores
Bianchini, Michele; de Brasi, Carlos Daniel; Gargallo, Patricia Martha; Gonzalez, Mariana Selena; Bengió, Raquel; Larripa, Irene Beatriz
Año de publicación
2009
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Imatinib mesylate has proven to be the most effective treatment in chronic myeloid leukemia. Nevertheless, imatinib resistance has raised concern and prompted interest in additional strategies to achieve disease eradication. Resistance to imatinib is mainly associated with three mechanisms: acquired mutations in the kinase domain of BCR-ABL protein, genetic amplification, and transcript overexpression of BCR-ABL rearrangement. Therefore an accurate assessment of resistance mechanism is particularly important to improve strategies to overcome resistance. In order to determine overexpression of BCR-ABL, we propose a method that correlates quantitative real time PCR and fluorescence in situ hybridization data from the same peripheral blood sample. The ratio between both methodologies permits to calculate the expression index (EI) for each patient. EI estimates the rate of BCR-ABL transcription per rearrangement. The median EI value, including all cases (n = 123), was 0.288; those cases (n = 13) included in percentile 90 showed an increment of EI above 1 Log (>2.88) with respect to the median value and were considered as cases with overexpression. We also evaluated the EIs using receiver operating characteristics curve; choosing an EI cutoff of 1.836 we obtained a sensitivity of 95% and a specificity of 61%. Using this EI cutoff value, more patients (n = 17) were included in the overexpression group. Patients within this group were resistant to imatinib and also showed a worse overall survival if compared with the remaining. © 2009 Blackwell Munksgaard.
Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Materia
Bcr-Abl
Chronic Myeloid Leukemia
Imatinib Mesylate
Overexpression
Treatment 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:11336/55974
Acceder
id CONICETDig_7e5c7152928bcadb42b7767b1b210368
oai_identifier_str oai:ri.conicet.gov.ar:11336/55974
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patientsBianchini, Michelede Brasi, Carlos DanielGargallo, Patricia MarthaGonzalez, Mariana SelenaBengió, RaquelLarripa, Irene BeatrizBcr-AblChronic Myeloid LeukemiaImatinib MesylateOverexpressionTreatment Resistancehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Imatinib mesylate has proven to be the most effective treatment in chronic myeloid leukemia. Nevertheless, imatinib resistance has raised concern and prompted interest in additional strategies to achieve disease eradication. Resistance to imatinib is mainly associated with three mechanisms: acquired mutations in the kinase domain of BCR-ABL protein, genetic amplification, and transcript overexpression of BCR-ABL rearrangement. Therefore an accurate assessment of resistance mechanism is particularly important to improve strategies to overcome resistance. In order to determine overexpression of BCR-ABL, we propose a method that correlates quantitative real time PCR and fluorescence in situ hybridization data from the same peripheral blood sample. The ratio between both methodologies permits to calculate the expression index (EI) for each patient. EI estimates the rate of BCR-ABL transcription per rearrangement. The median EI value, including all cases (n = 123), was 0.288; those cases (n = 13) included in percentile 90 showed an increment of EI above 1 Log (>2.88) with respect to the median value and were considered as cases with overexpression. We also evaluated the EIs using receiver operating characteristics curve; choosing an EI cutoff of 1.836 we obtained a sensitivity of 95% and a specificity of 61%. Using this EI cutoff value, more patients (n = 17) were included in the overexpression group. Patients within this group were resistant to imatinib and also showed a worse overall survival if compared with the remaining. © 2009 Blackwell Munksgaard.Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaWiley Blackwell Publishing, Inc2009-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/55974Bianchini, Michele; de Brasi, Carlos Daniel; Gargallo, Patricia Martha; Gonzalez, Mariana Selena; Bengió, Raquel; et al.; Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 82; 4; 4-2009; 292-3000902-4441CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1600-0609.2008.01199.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0609.2008.01199.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:59Zoai:ri.conicet.gov.ar:11336/55974instacron: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 09:55:59.967CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
title Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
spellingShingle Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
Bianchini, Michele
Bcr-Abl
Chronic Myeloid Leukemia
Imatinib Mesylate
Overexpression
Treatment Resistance
title_short Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
title_full Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
title_fullStr Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
title_full_unstemmed Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
title_sort Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients
dc.creator.none.fl_str_mv Bianchini, Michele
de Brasi, Carlos Daniel
Gargallo, Patricia Martha
Gonzalez, Mariana Selena
Bengió, Raquel
Larripa, Irene Beatriz
author Bianchini, Michele
author_facet Bianchini, Michele
de Brasi, Carlos Daniel
Gargallo, Patricia Martha
Gonzalez, Mariana Selena
Bengió, Raquel
Larripa, Irene Beatriz
author_role author
author2 de Brasi, Carlos Daniel
Gargallo, Patricia Martha
Gonzalez, Mariana Selena
Bengió, Raquel
Larripa, Irene Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Bcr-Abl
Chronic Myeloid Leukemia
Imatinib Mesylate
Overexpression
Treatment Resistance
topic Bcr-Abl
Chronic Myeloid Leukemia
Imatinib Mesylate
Overexpression
Treatment 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 Imatinib mesylate has proven to be the most effective treatment in chronic myeloid leukemia. Nevertheless, imatinib resistance has raised concern and prompted interest in additional strategies to achieve disease eradication. Resistance to imatinib is mainly associated with three mechanisms: acquired mutations in the kinase domain of BCR-ABL protein, genetic amplification, and transcript overexpression of BCR-ABL rearrangement. Therefore an accurate assessment of resistance mechanism is particularly important to improve strategies to overcome resistance. In order to determine overexpression of BCR-ABL, we propose a method that correlates quantitative real time PCR and fluorescence in situ hybridization data from the same peripheral blood sample. The ratio between both methodologies permits to calculate the expression index (EI) for each patient. EI estimates the rate of BCR-ABL transcription per rearrangement. The median EI value, including all cases (n = 123), was 0.288; those cases (n = 13) included in percentile 90 showed an increment of EI above 1 Log (>2.88) with respect to the median value and were considered as cases with overexpression. We also evaluated the EIs using receiver operating characteristics curve; choosing an EI cutoff of 1.836 we obtained a sensitivity of 95% and a specificity of 61%. Using this EI cutoff value, more patients (n = 17) were included in the overexpression group. Patients within this group were resistant to imatinib and also showed a worse overall survival if compared with the remaining. © 2009 Blackwell Munksgaard.
Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
description Imatinib mesylate has proven to be the most effective treatment in chronic myeloid leukemia. Nevertheless, imatinib resistance has raised concern and prompted interest in additional strategies to achieve disease eradication. Resistance to imatinib is mainly associated with three mechanisms: acquired mutations in the kinase domain of BCR-ABL protein, genetic amplification, and transcript overexpression of BCR-ABL rearrangement. Therefore an accurate assessment of resistance mechanism is particularly important to improve strategies to overcome resistance. In order to determine overexpression of BCR-ABL, we propose a method that correlates quantitative real time PCR and fluorescence in situ hybridization data from the same peripheral blood sample. The ratio between both methodologies permits to calculate the expression index (EI) for each patient. EI estimates the rate of BCR-ABL transcription per rearrangement. The median EI value, including all cases (n = 123), was 0.288; those cases (n = 13) included in percentile 90 showed an increment of EI above 1 Log (>2.88) with respect to the median value and were considered as cases with overexpression. We also evaluated the EIs using receiver operating characteristics curve; choosing an EI cutoff of 1.836 we obtained a sensitivity of 95% and a specificity of 61%. Using this EI cutoff value, more patients (n = 17) were included in the overexpression group. Patients within this group were resistant to imatinib and also showed a worse overall survival if compared with the remaining. © 2009 Blackwell Munksgaard.
publishDate 2009
dc.date.none.fl_str_mv 2009-04
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/11336/55974
Bianchini, Michele; de Brasi, Carlos Daniel; Gargallo, Patricia Martha; Gonzalez, Mariana Selena; Bengió, Raquel; et al.; Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 82; 4; 4-2009; 292-300
0902-4441
CONICET Digital
CONICET
url http://hdl.handle.net/11336/55974
identifier_str_mv Bianchini, Michele; de Brasi, Carlos Daniel; Gargallo, Patricia Martha; Gonzalez, Mariana Selena; Bengió, Raquel; et al.; Specific assessment of BCR-ABL transcript overexpression and imatinib resistance in chronic myeloid leukemia patients; Wiley Blackwell Publishing, Inc; European Journal Of Haematology; 82; 4; 4-2009; 292-300
0902-4441
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1600-0609.2008.01199.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1600-0609.2008.01199.x
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
publisher.none.fl_str_mv Wiley Blackwell Publishing, Inc
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
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