New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?

Autores
Noriega, Maria Fernanda; Ferri, Cristian Alberto; Icardi, Gustavo; Bullorsky, Eduardo; Korin, Jorge; Larripa, Irene Beatriz
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In chronic myeloid leukemia (CML) the presence of mutations in the tyrosine kinase domain (TK) of the normalABL1 gene is the most common cause of loss of response to treatment. Detection of these mutations is an important study because it allows the choice of most suitable TK inhibitor. We report a new mutation L324M that has not been detected so far. It is a case of a 44 year old male with CML chronic phase diagnosis in February 1996, who was treated from 2001 to 2006 with Imatinib. From February 2006 to May 2011 he was treated with decreasing doses of Dasatinib due to intolerance to the drug. At that time the patient showed loss of cytogenetic response and the presence of the mutation L324M by direct sequencing. Because of these finding, treatment was changed to 600 mg/day Nilotinib. After three months of treatment the mutation becomes undetectable and major molecular response (BCR-ABL1<0.1%) was achieved at 12 months. Our data suggest that the L324M mutation is sensitive to Nilotinib treatment.
Fil: Noriega, Maria Fernanda. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina
Fil: Ferri, Cristian Alberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Icardi, Gustavo. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina
Fil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; Argentina
Fil: Korin, Jorge. Consultorios Hematológicos S.R.L.; 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 "Mariano R. Castex". Departamento de Genética; Argentina
Materia
CML
Mutation
tyrosine kinase
Resistance
tyrosine kinase
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:11336/102282
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/102282
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?Noriega, Maria FernandaFerri, Cristian AlbertoIcardi, GustavoBullorsky, EduardoKorin, JorgeLarripa, Irene BeatrizCMLMutationtyrosine kinaseResistancetyrosine kinasehttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3In chronic myeloid leukemia (CML) the presence of mutations in the tyrosine kinase domain (TK) of the normalABL1 gene is the most common cause of loss of response to treatment. Detection of these mutations is an important study because it allows the choice of most suitable TK inhibitor. We report a new mutation L324M that has not been detected so far. It is a case of a 44 year old male with CML chronic phase diagnosis in February 1996, who was treated from 2001 to 2006 with Imatinib. From February 2006 to May 2011 he was treated with decreasing doses of Dasatinib due to intolerance to the drug. At that time the patient showed loss of cytogenetic response and the presence of the mutation L324M by direct sequencing. Because of these finding, treatment was changed to 600 mg/day Nilotinib. After three months of treatment the mutation becomes undetectable and major molecular response (BCR-ABL1<0.1%) was achieved at 12 months. Our data suggest that the L324M mutation is sensitive to Nilotinib treatment.Fil: Noriega, Maria Fernanda. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; ArgentinaFil: Ferri, Cristian Alberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Icardi, Gustavo. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; ArgentinaFil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; ArgentinaFil: Korin, Jorge. Consultorios Hematológicos S.R.L.; 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 "Mariano R. Castex". Departamento de Genética; ArgentinaTaylor & Francis Ltd2014-03info: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/11336/102282Noriega, Maria Fernanda; Ferri, Cristian Alberto; Icardi, Gustavo; Bullorsky, Eduardo; Korin, Jorge; et al.; New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?; Taylor & Francis Ltd; Leukemia and Lymphoma; 55; 3; 3-2014; 698-7011042-8194CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3109/10428194.2013.810735info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/10428194.2013.810735info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-05T09:59:23Zoai:ri.conicet.gov.ar:11336/102282instacron: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:34982025-11-05 09:59:23.784CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
title New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
spellingShingle New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
Noriega, Maria Fernanda
CML
Mutation
tyrosine kinase
Resistance
tyrosine kinase
title_short New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
title_full New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
title_fullStr New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
title_full_unstemmed New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
title_sort New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?
dc.creator.none.fl_str_mv Noriega, Maria Fernanda
Ferri, Cristian Alberto
Icardi, Gustavo
Bullorsky, Eduardo
Korin, Jorge
Larripa, Irene Beatriz
author Noriega, Maria Fernanda
author_facet Noriega, Maria Fernanda
Ferri, Cristian Alberto
Icardi, Gustavo
Bullorsky, Eduardo
Korin, Jorge
Larripa, Irene Beatriz
author_role author
author2 Ferri, Cristian Alberto
Icardi, Gustavo
Bullorsky, Eduardo
Korin, Jorge
Larripa, Irene Beatriz
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv CML
Mutation
tyrosine kinase
Resistance
tyrosine kinase
topic CML
Mutation
tyrosine kinase
Resistance
tyrosine kinase
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In chronic myeloid leukemia (CML) the presence of mutations in the tyrosine kinase domain (TK) of the normalABL1 gene is the most common cause of loss of response to treatment. Detection of these mutations is an important study because it allows the choice of most suitable TK inhibitor. We report a new mutation L324M that has not been detected so far. It is a case of a 44 year old male with CML chronic phase diagnosis in February 1996, who was treated from 2001 to 2006 with Imatinib. From February 2006 to May 2011 he was treated with decreasing doses of Dasatinib due to intolerance to the drug. At that time the patient showed loss of cytogenetic response and the presence of the mutation L324M by direct sequencing. Because of these finding, treatment was changed to 600 mg/day Nilotinib. After three months of treatment the mutation becomes undetectable and major molecular response (BCR-ABL1<0.1%) was achieved at 12 months. Our data suggest that the L324M mutation is sensitive to Nilotinib treatment.
Fil: Noriega, Maria Fernanda. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina
Fil: Ferri, Cristian Alberto. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentina
Fil: Icardi, Gustavo. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex". Departamento de Genética; Argentina
Fil: Bullorsky, Eduardo. Hospital Británico de Buenos Aires; Argentina
Fil: Korin, Jorge. Consultorios Hematológicos S.R.L.; 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 "Mariano R. Castex". Departamento de Genética; Argentina
description In chronic myeloid leukemia (CML) the presence of mutations in the tyrosine kinase domain (TK) of the normalABL1 gene is the most common cause of loss of response to treatment. Detection of these mutations is an important study because it allows the choice of most suitable TK inhibitor. We report a new mutation L324M that has not been detected so far. It is a case of a 44 year old male with CML chronic phase diagnosis in February 1996, who was treated from 2001 to 2006 with Imatinib. From February 2006 to May 2011 he was treated with decreasing doses of Dasatinib due to intolerance to the drug. At that time the patient showed loss of cytogenetic response and the presence of the mutation L324M by direct sequencing. Because of these finding, treatment was changed to 600 mg/day Nilotinib. After three months of treatment the mutation becomes undetectable and major molecular response (BCR-ABL1<0.1%) was achieved at 12 months. Our data suggest that the L324M mutation is sensitive to Nilotinib treatment.
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/11336/102282
Noriega, Maria Fernanda; Ferri, Cristian Alberto; Icardi, Gustavo; Bullorsky, Eduardo; Korin, Jorge; et al.; New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?; Taylor & Francis Ltd; Leukemia and Lymphoma; 55; 3; 3-2014; 698-701
1042-8194
CONICET Digital
CONICET
url http://hdl.handle.net/11336/102282
identifier_str_mv Noriega, Maria Fernanda; Ferri, Cristian Alberto; Icardi, Gustavo; Bullorsky, Eduardo; Korin, Jorge; et al.; New mutation L324M in the ABL1 kinase domain: does it confer high resistance to second-generation inhibitors?; Taylor & Francis Ltd; Leukemia and Lymphoma; 55; 3; 3-2014; 698-701
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/10.3109/10428194.2013.810735
info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/abs/10.3109/10428194.2013.810735
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 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
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score 13.084122

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