CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease

Autores
Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Ferri, Cristian Alberto; Bengió, Raquel; Bianchini, Michele; Larripa, Irene Beatriz
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Patients with chronic myeloid leukemia (CML) can develop disease resistance to tyrosine kinase inhibitor (TKI) therapy, which is mainly attributable to the presence of point mutations in the tyrosine kinase domain of BCR–ABL1. In order to examine suitable markers to monitor treatment efficacy, we investigated transcript expression profiles of genes known to be involved in myeloid cell proliferation, such as CAMKIIγ and KI67, and in protein stability and ultimately cell survival under physiological and stress conditions, such as heat shock proteins HSP70 and HSP90. We studied 101 patients with CML in different stages of disease and with different responses to TKI treatment. The results of quantitative real-time polymerase chain reaction (qPCR) analyses showed that the expression levels of CAMKIIγ, KI67, HSP70 and HSP90 genes were up-regulated at diagnosis, and in cases with signs of treatment resistance both in chronic and advanced phases (accelerated and blastic phases) with respect to chronic phase in remission and healthy donors. When only 56 resistant cases, 31 with mutations (MT) and 25 without mutations (WT), in the BCR–ABL1 tyrosine kinase domain were considered, the transcript expression profile showed an unexpected significant increase in CAMKIIγ and HSP70, and a significant decrease in HSP90 in MT versus WT cases. This differential transcript expression prompted us to design an expression score, log(CAMKIIγ × HSP70/HSP90), which can be used to provide rapid screening to discriminate the presence or absence of mutations in resistant cells and to monitor TKI treatment efficacy in patients with CML.
Fil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Materia
Chronic Myeloid Leukemia
Bcr-Abl1
Camkiiγ
Hsp70
Hsp90
Gene Expression
Mutations
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:11336/35902
Acceder
id CONICETDig_70b13544f65e222d438ef022ea23581a
oai_identifier_str oai:ri.conicet.gov.ar:11336/35902
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated diseaseGonzalez, Mariana Selenade Brasi, Carlos DanielFerri, Cristian AlbertoBengió, RaquelBianchini, MicheleLarripa, Irene BeatrizChronic Myeloid LeukemiaBcr-Abl1CamkiiγHsp70Hsp90Gene ExpressionMutationshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Patients with chronic myeloid leukemia (CML) can develop disease resistance to tyrosine kinase inhibitor (TKI) therapy, which is mainly attributable to the presence of point mutations in the tyrosine kinase domain of BCR–ABL1. In order to examine suitable markers to monitor treatment efficacy, we investigated transcript expression profiles of genes known to be involved in myeloid cell proliferation, such as CAMKIIγ and KI67, and in protein stability and ultimately cell survival under physiological and stress conditions, such as heat shock proteins HSP70 and HSP90. We studied 101 patients with CML in different stages of disease and with different responses to TKI treatment. The results of quantitative real-time polymerase chain reaction (qPCR) analyses showed that the expression levels of CAMKIIγ, KI67, HSP70 and HSP90 genes were up-regulated at diagnosis, and in cases with signs of treatment resistance both in chronic and advanced phases (accelerated and blastic phases) with respect to chronic phase in remission and healthy donors. When only 56 resistant cases, 31 with mutations (MT) and 25 without mutations (WT), in the BCR–ABL1 tyrosine kinase domain were considered, the transcript expression profile showed an unexpected significant increase in CAMKIIγ and HSP70, and a significant decrease in HSP90 in MT versus WT cases. This differential transcript expression prompted us to design an expression score, log(CAMKIIγ × HSP70/HSP90), which can be used to provide rapid screening to discriminate the presence or absence of mutations in resistant cells and to monitor TKI treatment efficacy in patients with CML.Fil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaFil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; ArgentinaFil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; ArgentinaTaylor & Francis2014-03info: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/11336/35902Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Ferri, Cristian Alberto; Bengió, Raquel; Bianchini, Michele; et al.; CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease; Taylor & Francis; Leukemia and Lymphoma; 55; 9; 3-2014; 2101-21081042-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2013.861070info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/10428194.2013.861070info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:08:07Zoai:ri.conicet.gov.ar:11336/35902instacron: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 10:08:07.389CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
title CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
spellingShingle CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
Gonzalez, Mariana Selena
Chronic Myeloid Leukemia
Bcr-Abl1
Camkiiγ
Hsp70
Hsp90
Gene Expression
Mutations
title_short CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
title_full CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
title_fullStr CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
title_full_unstemmed CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
title_sort CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease
dc.creator.none.fl_str_mv Gonzalez, Mariana Selena
de Brasi, Carlos Daniel
Ferri, Cristian Alberto
Bengió, Raquel
Bianchini, Michele
Larripa, Irene Beatriz
author Gonzalez, Mariana Selena
author_facet Gonzalez, Mariana Selena
de Brasi, Carlos Daniel
Ferri, Cristian Alberto
Bengió, Raquel
Bianchini, Michele
Larripa, Irene Beatriz
author_role author
author2 de Brasi, Carlos Daniel
Ferri, Cristian Alberto
Bengió, Raquel
Bianchini, Michele
Larripa, Irene Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Chronic Myeloid Leukemia
Bcr-Abl1
Camkiiγ
Hsp70
Hsp90
Gene Expression
Mutations
topic Chronic Myeloid Leukemia
Bcr-Abl1
Camkiiγ
Hsp70
Hsp90
Gene Expression
Mutations
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Patients with chronic myeloid leukemia (CML) can develop disease resistance to tyrosine kinase inhibitor (TKI) therapy, which is mainly attributable to the presence of point mutations in the tyrosine kinase domain of BCR–ABL1. In order to examine suitable markers to monitor treatment efficacy, we investigated transcript expression profiles of genes known to be involved in myeloid cell proliferation, such as CAMKIIγ and KI67, and in protein stability and ultimately cell survival under physiological and stress conditions, such as heat shock proteins HSP70 and HSP90. We studied 101 patients with CML in different stages of disease and with different responses to TKI treatment. The results of quantitative real-time polymerase chain reaction (qPCR) analyses showed that the expression levels of CAMKIIγ, KI67, HSP70 and HSP90 genes were up-regulated at diagnosis, and in cases with signs of treatment resistance both in chronic and advanced phases (accelerated and blastic phases) with respect to chronic phase in remission and healthy donors. When only 56 resistant cases, 31 with mutations (MT) and 25 without mutations (WT), in the BCR–ABL1 tyrosine kinase domain were considered, the transcript expression profile showed an unexpected significant increase in CAMKIIγ and HSP70, and a significant decrease in HSP90 in MT versus WT cases. This differential transcript expression prompted us to design an expression score, log(CAMKIIγ × HSP70/HSP90), which can be used to provide rapid screening to discriminate the presence or absence of mutations in resistant cells and to monitor TKI treatment efficacy in patients with CML.
Fil: Gonzalez, Mariana Selena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: de Brasi, Carlos Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Ferri, Cristian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Bengió, Raquel. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
Fil: Bianchini, Michele. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Fundación Cáncer. Centro de Investigaciones Oncológicas; Argentina
Fil: Larripa, Irene Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas ; Argentina
description Patients with chronic myeloid leukemia (CML) can develop disease resistance to tyrosine kinase inhibitor (TKI) therapy, which is mainly attributable to the presence of point mutations in the tyrosine kinase domain of BCR–ABL1. In order to examine suitable markers to monitor treatment efficacy, we investigated transcript expression profiles of genes known to be involved in myeloid cell proliferation, such as CAMKIIγ and KI67, and in protein stability and ultimately cell survival under physiological and stress conditions, such as heat shock proteins HSP70 and HSP90. We studied 101 patients with CML in different stages of disease and with different responses to TKI treatment. The results of quantitative real-time polymerase chain reaction (qPCR) analyses showed that the expression levels of CAMKIIγ, KI67, HSP70 and HSP90 genes were up-regulated at diagnosis, and in cases with signs of treatment resistance both in chronic and advanced phases (accelerated and blastic phases) with respect to chronic phase in remission and healthy donors. When only 56 resistant cases, 31 with mutations (MT) and 25 without mutations (WT), in the BCR–ABL1 tyrosine kinase domain were considered, the transcript expression profile showed an unexpected significant increase in CAMKIIγ and HSP70, and a significant decrease in HSP90 in MT versus WT cases. This differential transcript expression prompted us to design an expression score, log(CAMKIIγ × HSP70/HSP90), which can be used to provide rapid screening to discriminate the presence or absence of mutations in resistant cells and to monitor TKI treatment efficacy in patients with CML.
publishDate 2014
dc.date.none.fl_str_mv 2014-03
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/11336/35902
Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Ferri, Cristian Alberto; Bengió, Raquel; Bianchini, Michele; et al.; CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease; Taylor & Francis; Leukemia and Lymphoma; 55; 9; 3-2014; 2101-2108
1042-8194
CONICET Digital
CONICET
url http://hdl.handle.net/11336/35902
identifier_str_mv Gonzalez, Mariana Selena; de Brasi, Carlos Daniel; Ferri, Cristian Alberto; Bengió, Raquel; Bianchini, Michele; et al.; CAMKIIγ, HSP70 and HSP90 transcripts are differentially expressed in chronic myeloid leukemia cells from patients with resistant mutated disease; Taylor & Francis; Leukemia and Lymphoma; 55; 9; 3-2014; 2101-2108
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/doi/10.3109/10428194.2013.861070
info:eu-repo/semantics/altIdentifier/url/http://www.tandfonline.com/doi/full/10.3109/10428194.2013.861070
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 Taylor & Francis
publisher.none.fl_str_mv Taylor & Francis
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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