BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , |
Tipo de documento: | Artigo |
Idioma: | por |
Título da fonte: | Revista Ciências em Saúde |
Texto Completo: | https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994 |
Resumo: | Objective: Chronic Myeloid Leukemia (CML) is a clonal disorder of hematopoietic progenitor cells, characterized by a reciprocal translocation between chromosomes 9 and 22, which results in the hybrid gene BCR-ABL1. Even with the progress in the treatment of the disease allowed by tyrosine kinase inhibitors, point mutations in this gene's domain are the main causes of therapeutic resistance, mainly to imatinib mesylate. This study aimed to analyze the point mutations of high resistance in a patient with CML and its possible correlation with treatment response. Methods: Cross-sectional study with 58 CML patients undergoing treatment with imatinib and with suboptimal response to therapy. Blood samples were analyzed by real-time PCR using TaqMan® chemistry to evaluate the following point mutations: T315I, E255V and Y253H. Results: None of the 58 patients had any of the investigated mutations. There was irregular use of the medication in 16% (n = 9), of which 44% (n = 4) reported discontinuous use and interruption on their own, and 56% (n = 5) showed intolerance to treatment and switched drugs. Conclusion: The absence of point mutations in CML patients analyzed in this study demonstrated that failure in therapy has no molecular correlation with the analyzed mutations and may be related to lower treatment adherence rates. These findings were demonstrated in a considerable number of evaluated patients, pointing out the need for education on the importance of following the recommendations on their treatment to avoid future complications. |
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BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylateAnálise de mutações do domínio BCR-ABL quinase em pacientes com leucemia mielóide crônica refratários ao tratamento com mesilato de imatinibeantineoplasticsbcr-abl proto-oncogeneschronic myeloid leukemiaimatinib mesylatetherapeutic adherenceChronic myeloid leukemiaadesão terapêuticaantineoplásicosgenes ablleucemia mieloide crônicamesilato de imatinibeLeucemia mielóide crˆônicaObjective: Chronic Myeloid Leukemia (CML) is a clonal disorder of hematopoietic progenitor cells, characterized by a reciprocal translocation between chromosomes 9 and 22, which results in the hybrid gene BCR-ABL1. Even with the progress in the treatment of the disease allowed by tyrosine kinase inhibitors, point mutations in this gene's domain are the main causes of therapeutic resistance, mainly to imatinib mesylate. This study aimed to analyze the point mutations of high resistance in a patient with CML and its possible correlation with treatment response. Methods: Cross-sectional study with 58 CML patients undergoing treatment with imatinib and with suboptimal response to therapy. Blood samples were analyzed by real-time PCR using TaqMan® chemistry to evaluate the following point mutations: T315I, E255V and Y253H. Results: None of the 58 patients had any of the investigated mutations. There was irregular use of the medication in 16% (n = 9), of which 44% (n = 4) reported discontinuous use and interruption on their own, and 56% (n = 5) showed intolerance to treatment and switched drugs. Conclusion: The absence of point mutations in CML patients analyzed in this study demonstrated that failure in therapy has no molecular correlation with the analyzed mutations and may be related to lower treatment adherence rates. These findings were demonstrated in a considerable number of evaluated patients, pointing out the need for education on the importance of following the recommendations on their treatment to avoid future complications.Objetivo: A Leucemia Mielóide Crônica (LMC) é um distúrbio clonal de células progenitoras hematopoiéticas, caracterizada por uma translocação recíproca entre os cromossomos 9 e 22, que resulta no gene híbrido BCR-ABL1.Mesmo com o progresso no tratamento da doença permitido pelos inibidores de tirosina quinase, mutações pontuais no domínio desse gene são as principais causas de resistência terapêutica, principalmente ao mesilato de imatinibe. O objetivo desse estudo foi analisar as mutações pontuais de alta resistência em paciente com LMC e sua possível correlação com a resposta ao tratamento. Métodos: Estudo transversal com 58 pacientes com LMC em tratamento com imatinibe e com resposta subótima à terapia. As amostras de sangue foram analisadas por PCR em tempo real usando a química TaqMan® para avaliar as seguintes mutações pontuais: T315I, E255V e Y253H. Resultados: Nenhum dos 58 pacientes apresentou alguma das mutações investigadas. Houve uso irregular da medicação em 16% (n = 9), dos quais 44% (n = 4) relataram uso descontínuo e interrupção por conta própria, e 56% (n = 5) apresentaram intolerância ao tratamento e trocaram de fármaco. Conclusão: A ausência das mutações pontuais nos pacientes portadores de LMC analisados neste estudo demonstrou que a falha na terapia não tem correlação molecular com as mutações analisadas e pode estar relacionada à menores taxas de adesão ao tratamento. Estes achados foram demonstrados em um número considerável de pacientes avaliados, apontando a necessidade da edução sobre a importância de seguir as recomendações sobre seu tratamento para evitar complicações futuras.AISI/HCI2020-12-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionPeer reviewedAvaliado pelos parestextoinfo:eu-repo/semantics/otherapplication/pdfhttps://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/99410.21876/rcshci.v10i4.994Revista Ciências em Saúde; v. 10 n. 4 (2020): Outubro a Dezembro de 2020; 77-84Health Sciences Journal; Vol 10 No 4 (2020): October to December 2020; 77-842236-378510.21876/rcshci.v10i4reponame:Revista Ciências em Saúdeinstname:Hospital de Clínicas de Itajubáinstacron:HCIporhttps://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994/616Copyright (c) 2020 REVISTA CIÊNCIAS EM SAÚDEhttps://creativecommons.org/licenses/by-nc-sa/4.0info:eu-repo/semantics/openAccessPinto, Laine Celestino Sales, Lívia de Oliveira Azevedo, Tereza Cristina de BritoMoreira-Nunes, Caroline AquinoLemos, José Alexandre Rodrigues2020-12-19T07:46:47Zoai:ojs.portalrcs.hcitajuba.org.br:article/994Revistahttps://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zeroPUBhttps://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/oaircs@hcitajuba.org.br||rcsfmit@medicinaitajuba.com.br2236-37852236-3785opendoar:2020-12-19T07:46:47Revista Ciências em Saúde - Hospital de Clínicas de Itajubáfalse |
dc.title.none.fl_str_mv |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate Análise de mutações do domínio BCR-ABL quinase em pacientes com leucemia mielóide crônica refratários ao tratamento com mesilato de imatinibe |
title |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
spellingShingle |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate Pinto, Laine Celestino antineoplastics bcr-abl proto-oncogenes chronic myeloid leukemia imatinib mesylate therapeutic adherence Chronic myeloid leukemia adesão terapêutica antineoplásicos genes abl leucemia mieloide crônica mesilato de imatinibe Leucemia mielóide crˆônica |
title_short |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
title_full |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
title_fullStr |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
title_full_unstemmed |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
title_sort |
BCR-ABL kinase domain mutations analysis in chronic myeloid leukaemia patients that are not responsive to imatinib mesylate |
author |
Pinto, Laine Celestino |
author_facet |
Pinto, Laine Celestino Sales, Lívia de Oliveira Azevedo, Tereza Cristina de Brito Moreira-Nunes, Caroline Aquino Lemos, José Alexandre Rodrigues |
author_role |
author |
author2 |
Sales, Lívia de Oliveira Azevedo, Tereza Cristina de Brito Moreira-Nunes, Caroline Aquino Lemos, José Alexandre Rodrigues |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Pinto, Laine Celestino Sales, Lívia de Oliveira Azevedo, Tereza Cristina de Brito Moreira-Nunes, Caroline Aquino Lemos, José Alexandre Rodrigues |
dc.subject.por.fl_str_mv |
antineoplastics bcr-abl proto-oncogenes chronic myeloid leukemia imatinib mesylate therapeutic adherence Chronic myeloid leukemia adesão terapêutica antineoplásicos genes abl leucemia mieloide crônica mesilato de imatinibe Leucemia mielóide crˆônica |
topic |
antineoplastics bcr-abl proto-oncogenes chronic myeloid leukemia imatinib mesylate therapeutic adherence Chronic myeloid leukemia adesão terapêutica antineoplásicos genes abl leucemia mieloide crônica mesilato de imatinibe Leucemia mielóide crˆônica |
description |
Objective: Chronic Myeloid Leukemia (CML) is a clonal disorder of hematopoietic progenitor cells, characterized by a reciprocal translocation between chromosomes 9 and 22, which results in the hybrid gene BCR-ABL1. Even with the progress in the treatment of the disease allowed by tyrosine kinase inhibitors, point mutations in this gene's domain are the main causes of therapeutic resistance, mainly to imatinib mesylate. This study aimed to analyze the point mutations of high resistance in a patient with CML and its possible correlation with treatment response. Methods: Cross-sectional study with 58 CML patients undergoing treatment with imatinib and with suboptimal response to therapy. Blood samples were analyzed by real-time PCR using TaqMan® chemistry to evaluate the following point mutations: T315I, E255V and Y253H. Results: None of the 58 patients had any of the investigated mutations. There was irregular use of the medication in 16% (n = 9), of which 44% (n = 4) reported discontinuous use and interruption on their own, and 56% (n = 5) showed intolerance to treatment and switched drugs. Conclusion: The absence of point mutations in CML patients analyzed in this study demonstrated that failure in therapy has no molecular correlation with the analyzed mutations and may be related to lower treatment adherence rates. These findings were demonstrated in a considerable number of evaluated patients, pointing out the need for education on the importance of following the recommendations on their treatment to avoid future complications. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-10 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Peer reviewed Avaliado pelos pares texto info:eu-repo/semantics/other |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994 10.21876/rcshci.v10i4.994 |
url |
https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994 |
identifier_str_mv |
10.21876/rcshci.v10i4.994 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.relation.none.fl_str_mv |
https://portalrcs.hcitajuba.org.br/index.php/rcsfmit_zero/article/view/994/616 |
dc.rights.driver.fl_str_mv |
Copyright (c) 2020 REVISTA CIÊNCIAS EM SAÚDE https://creativecommons.org/licenses/by-nc-sa/4.0 info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Copyright (c) 2020 REVISTA CIÊNCIAS EM SAÚDE https://creativecommons.org/licenses/by-nc-sa/4.0 |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
AISI/HCI |
publisher.none.fl_str_mv |
AISI/HCI |
dc.source.none.fl_str_mv |
Revista Ciências em Saúde; v. 10 n. 4 (2020): Outubro a Dezembro de 2020; 77-84 Health Sciences Journal; Vol 10 No 4 (2020): October to December 2020; 77-84 2236-3785 10.21876/rcshci.v10i4 reponame:Revista Ciências em Saúde instname:Hospital de Clínicas de Itajubá instacron:HCI |
instname_str |
Hospital de Clínicas de Itajubá |
instacron_str |
HCI |
institution |
HCI |
reponame_str |
Revista Ciências em Saúde |
collection |
Revista Ciências em Saúde |
repository.name.fl_str_mv |
Revista Ciências em Saúde - Hospital de Clínicas de Itajubá |
repository.mail.fl_str_mv |
rcs@hcitajuba.org.br||rcsfmit@medicinaitajuba.com.br |
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1797068962791424000 |