BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia

Autores
Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Bianchini, Michele; Gargallo, Patricia Martha; Moiraghi, Beatriz; Bengió, Raquel; Larripa, Irene Beatriz
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BCR-ABL fusion gene is implicated in the pathogenesis of chronic myeloid leukemia (CML), encoding the oncoprotein p210 BCR-ABL with an anti-apoptotic activity. The inability to undergo apoptosis is an important mechanism of drug resistance and neoplastic evolution in CML. The gene transcript expression of mitochondrial apoptotic related genes BAX and BCL-XL were evaluated by quantitative Real Time PCR (qPCR) in vitro in K562 cells and in vivo in peripheral blood of 66 CML patients in different stages of the disease: 13 cases at diagnosis, 34 in chronic phase (CP), 10 in accelerated phase (AP) and 9 in blast crisis (BC). Our results in K562 cells showed that all treatments with different tyrosine kinase inhibitors (TKIs) induced a decreased expression of the antiapoptotic oncogene BCL-XL, whereas the proapoptotic gene BAX remains constant with minor modifications. A significantly lower BAX/BCL-XL expression ratio (mean ± SEM) than a group of healthy individuals (4.8 ± 0.59) were observed in CML patients at diagnosis (1.28 ± 0.16), in AP (1.14 ± 0.20), in BC (1.16 ± 0.30) and in 18% of cases of patients in CP (2.71 ± 0.40). Most CP cases (82%) showed a significantly increased ratio (10.03 ± 1.30), indicating that the treatment with TKIs efficiently inhibited the expression of BCL-XL by blocking BCR-ABL oncoprotein. The BAX/BCL-XL ratio showed a significant inverse correlation (Spearman P< 0.0001) with BCR-ABL/ABL relative expression indicating that low BAX/BCL-XL associated with disease progression. Accordingly, the follow up of a cohort of eight cases during 6 months from diagnosis showed that while the BAX/BCL-XL ratio rapidly increased after treatment in seven cases with good evolution, it decreased in the only one case that showed  bad evolution and short survival. Our data suggest that BAX/BCL-XL expression ratio may be a sensitive monitor of disease progression and an early predictor of TKI therapy responsiveness in CML patients.
Fil: Gonzalez, Mariana Selena. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
chronic myeloid leukemia
BAX
BCL-XL
QRT-PCR
Apoptosis
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:11336/247020
Acceder
id CONICETDig_8e2b9af7dff1dd306549114c9b0227dd
oai_identifier_str oai:ri.conicet.gov.ar:11336/247020
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemiaGonzalez, Mariana Selenade Brasi, Carlos DanielBianchini, MicheleGargallo, Patricia MarthaMoiraghi, BeatrizBengió, RaquelLarripa, Irene Beatrizchronic myeloid leukemiaBAXBCL-XLQRT-PCRApoptosishttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3BCR-ABL fusion gene is implicated in the pathogenesis of chronic myeloid leukemia (CML), encoding the oncoprotein p210 BCR-ABL with an anti-apoptotic activity. The inability to undergo apoptosis is an important mechanism of drug resistance and neoplastic evolution in CML. The gene transcript expression of mitochondrial apoptotic related genes BAX and BCL-XL were evaluated by quantitative Real Time PCR (qPCR) in vitro in K562 cells and in vivo in peripheral blood of 66 CML patients in different stages of the disease: 13 cases at diagnosis, 34 in chronic phase (CP), 10 in accelerated phase (AP) and 9 in blast crisis (BC). Our results in K562 cells showed that all treatments with different tyrosine kinase inhibitors (TKIs) induced a decreased expression of the antiapoptotic oncogene BCL-XL, whereas the proapoptotic gene BAX remains constant with minor modifications. A significantly lower BAX/BCL-XL expression ratio (mean ± SEM) than a group of healthy individuals (4.8 ± 0.59) were observed in CML patients at diagnosis (1.28 ± 0.16), in AP (1.14 ± 0.20), in BC (1.16 ± 0.30) and in 18% of cases of patients in CP (2.71 ± 0.40). Most CP cases (82%) showed a significantly increased ratio (10.03 ± 1.30), indicating that the treatment with TKIs efficiently inhibited the expression of BCL-XL by blocking BCR-ABL oncoprotein. The BAX/BCL-XL ratio showed a significant inverse correlation (Spearman P< 0.0001) with BCR-ABL/ABL relative expression indicating that low BAX/BCL-XL associated with disease progression. Accordingly, the follow up of a cohort of eight cases during 6 months from diagnosis showed that while the BAX/BCL-XL ratio rapidly increased after treatment in seven cases with good evolution, it decreased in the only one case that showed  bad evolution and short survival. Our data suggest that BAX/BCL-XL expression ratio may be a sensitive monitor of disease progression and an early predictor of TKI therapy responsiveness in CML patients.Fil: Gonzalez, Mariana Selena. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; ArgentinaFil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAcademic Press Inc Elsevier Science2010-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/247020Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Bianchini, Michele; Gargallo, Patricia Martha; Moiraghi, Beatriz; et al.; BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 45; 3; 10-2010; 192-1961079-9796CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S1079979610001920info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcmd.2010.07.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:04:57Zoai:ri.conicet.gov.ar:11336/247020instacron: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:34982025-09-10 13:04:57.68CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
title BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
spellingShingle BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
Gonzalez, Mariana Selena
chronic myeloid leukemia
BAX
BCL-XL
QRT-PCR
Apoptosis
title_short BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
title_full BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
title_fullStr BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
title_full_unstemmed BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
title_sort BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia
dc.creator.none.fl_str_mv Gonzalez, Mariana Selena
de Brasi, Carlos Daniel
Bianchini, Michele
Gargallo, Patricia Martha
Moiraghi, Beatriz
Bengió, Raquel
Larripa, Irene Beatriz
author Gonzalez, Mariana Selena
author_facet Gonzalez, Mariana Selena
de Brasi, Carlos Daniel
Bianchini, Michele
Gargallo, Patricia Martha
Moiraghi, Beatriz
Bengió, Raquel
Larripa, Irene Beatriz
author_role author
author2 de Brasi, Carlos Daniel
Bianchini, Michele
Gargallo, Patricia Martha
Moiraghi, Beatriz
Bengió, Raquel
Larripa, Irene Beatriz
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv chronic myeloid leukemia
BAX
BCL-XL
QRT-PCR
Apoptosis
topic chronic myeloid leukemia
BAX
BCL-XL
QRT-PCR
Apoptosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BCR-ABL fusion gene is implicated in the pathogenesis of chronic myeloid leukemia (CML), encoding the oncoprotein p210 BCR-ABL with an anti-apoptotic activity. The inability to undergo apoptosis is an important mechanism of drug resistance and neoplastic evolution in CML. The gene transcript expression of mitochondrial apoptotic related genes BAX and BCL-XL were evaluated by quantitative Real Time PCR (qPCR) in vitro in K562 cells and in vivo in peripheral blood of 66 CML patients in different stages of the disease: 13 cases at diagnosis, 34 in chronic phase (CP), 10 in accelerated phase (AP) and 9 in blast crisis (BC). Our results in K562 cells showed that all treatments with different tyrosine kinase inhibitors (TKIs) induced a decreased expression of the antiapoptotic oncogene BCL-XL, whereas the proapoptotic gene BAX remains constant with minor modifications. A significantly lower BAX/BCL-XL expression ratio (mean ± SEM) than a group of healthy individuals (4.8 ± 0.59) were observed in CML patients at diagnosis (1.28 ± 0.16), in AP (1.14 ± 0.20), in BC (1.16 ± 0.30) and in 18% of cases of patients in CP (2.71 ± 0.40). Most CP cases (82%) showed a significantly increased ratio (10.03 ± 1.30), indicating that the treatment with TKIs efficiently inhibited the expression of BCL-XL by blocking BCR-ABL oncoprotein. The BAX/BCL-XL ratio showed a significant inverse correlation (Spearman P< 0.0001) with BCR-ABL/ABL relative expression indicating that low BAX/BCL-XL associated with disease progression. Accordingly, the follow up of a cohort of eight cases during 6 months from diagnosis showed that while the BAX/BCL-XL ratio rapidly increased after treatment in seven cases with good evolution, it decreased in the only one case that showed  bad evolution and short survival. Our data suggest that BAX/BCL-XL expression ratio may be a sensitive monitor of disease progression and an early predictor of TKI therapy responsiveness in CML patients.
Fil: Gonzalez, Mariana Selena. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: de Brasi, Carlos Daniel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Bianchini, Michele. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Gargallo, Patricia Martha. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Moiraghi, Beatriz. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Ramos Mejía"; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina
Fil: Larripa, Irene Beatriz. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description BCR-ABL fusion gene is implicated in the pathogenesis of chronic myeloid leukemia (CML), encoding the oncoprotein p210 BCR-ABL with an anti-apoptotic activity. The inability to undergo apoptosis is an important mechanism of drug resistance and neoplastic evolution in CML. The gene transcript expression of mitochondrial apoptotic related genes BAX and BCL-XL were evaluated by quantitative Real Time PCR (qPCR) in vitro in K562 cells and in vivo in peripheral blood of 66 CML patients in different stages of the disease: 13 cases at diagnosis, 34 in chronic phase (CP), 10 in accelerated phase (AP) and 9 in blast crisis (BC). Our results in K562 cells showed that all treatments with different tyrosine kinase inhibitors (TKIs) induced a decreased expression of the antiapoptotic oncogene BCL-XL, whereas the proapoptotic gene BAX remains constant with minor modifications. A significantly lower BAX/BCL-XL expression ratio (mean ± SEM) than a group of healthy individuals (4.8 ± 0.59) were observed in CML patients at diagnosis (1.28 ± 0.16), in AP (1.14 ± 0.20), in BC (1.16 ± 0.30) and in 18% of cases of patients in CP (2.71 ± 0.40). Most CP cases (82%) showed a significantly increased ratio (10.03 ± 1.30), indicating that the treatment with TKIs efficiently inhibited the expression of BCL-XL by blocking BCR-ABL oncoprotein. The BAX/BCL-XL ratio showed a significant inverse correlation (Spearman P< 0.0001) with BCR-ABL/ABL relative expression indicating that low BAX/BCL-XL associated with disease progression. Accordingly, the follow up of a cohort of eight cases during 6 months from diagnosis showed that while the BAX/BCL-XL ratio rapidly increased after treatment in seven cases with good evolution, it decreased in the only one case that showed  bad evolution and short survival. Our data suggest that BAX/BCL-XL expression ratio may be a sensitive monitor of disease progression and an early predictor of TKI therapy responsiveness in CML patients.
publishDate 2010
dc.date.none.fl_str_mv 2010-10
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/11336/247020
Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Bianchini, Michele; Gargallo, Patricia Martha; Moiraghi, Beatriz; et al.; BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 45; 3; 10-2010; 192-196
1079-9796
CONICET Digital
CONICET
url http://hdl.handle.net/11336/247020
identifier_str_mv Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Bianchini, Michele; Gargallo, Patricia Martha; Moiraghi, Beatriz; et al.; BAX/BCL-XL gene expression ratio inversely correlates with disease progression in chronic myeloid leukemia; Academic Press Inc Elsevier Science; Blood Cells Molecules And Diseases; 45; 3; 10-2010; 192-196
1079-9796
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.sciencedirect.com/science/article/pii/S1079979610001920
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bcmd.2010.07.011
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
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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score 12.993085

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