A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/127779 |
Resumo: | cofinanced by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). Inn-INDIGO/0002/2015. |
| id |
RCAP_ee892a87d17c76f5a957ebdf74275048 |
|---|---|
| oai_identifier_str |
oai:run.unl.pt:10362/127779 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemiaALLE14a2MutationP.Y440CPhiladelphia chromosomeOncologyPharmacology (medical)SDG 3 - Good Health and Well-beingcofinanced by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). Inn-INDIGO/0002/2015.Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) represents the most common genetic subtype of adult ALL (20%–30%) and accounts for approximately 50% of all cases in the elderly. It has been considered the subgroup of ALL with the worst outcome. The introduction of tyrosine kinase inhibitors (TKIs) allows complete hematologic remission virtually in all patients, with improved disease-free survival and overall survival. Nevertheless, the emergence of resistant mutations in BCR-ABL1 may require different TKI strategies to overcome the patient’s resistance and disease relapse. Here, we report a Ph+ B-ALL case with persistent minimal residual disease (MRD) after treatment with dasatinib. The patient expressed the P190BCR-ABL1 isoform and a novel BCR-ABL1 mutation, p.Y440C. The latter is in the C-terminal lobe of the kinase domain, which likely induces deviations in the protein structure and activity and destabilizes its inactive conformation. The treatment was substituted by bosutinib, which binds to the active conformation of the protein, prior to allogeneic bone marrow transplant to overcome the lack of a complete response to dasatinib. These findings strengthen the importance of BCR-ABL1 mutational screening in Ph+ patients, particularly for those who do not achieve complete molecular remission.UCIBIO - Applied Molecular Biosciences UnitDCV - Departamento de Ciências da VidaRUNVinhas, RaquelLourenço, AlexandraSantos, SusanaLemos, MarcosRibeiro, Patríciade Sousa, Aida BotelhoBaptista, Pedro VianaFernandes, Alexandra Ramos2021-11-15T23:29:27Z2018-01-012018-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article10application/pdfhttp://hdl.handle.net/10362/127779eng1178-6930PURE: 10569353https://doi.org/10.2147/OTT.S177019info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:07:37Zoai:run.unl.pt:10362/127779Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:46:12.175883Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| title |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| spellingShingle |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia Vinhas, Raquel ALL E14a2 Mutation P.Y440C Philadelphia chromosome Oncology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| title_short |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| title_full |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| title_fullStr |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| title_full_unstemmed |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| title_sort |
A novel BCR-ABL1 mutation in a patient with philadelphia chromosome-positive B-cell acute lymphoblastic leukemia |
| author |
Vinhas, Raquel |
| author_facet |
Vinhas, Raquel Lourenço, Alexandra Santos, Susana Lemos, Marcos Ribeiro, Patrícia de Sousa, Aida Botelho Baptista, Pedro Viana Fernandes, Alexandra Ramos |
| author_role |
author |
| author2 |
Lourenço, Alexandra Santos, Susana Lemos, Marcos Ribeiro, Patrícia de Sousa, Aida Botelho Baptista, Pedro Viana Fernandes, Alexandra Ramos |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
UCIBIO - Applied Molecular Biosciences Unit DCV - Departamento de Ciências da Vida RUN |
| dc.contributor.author.fl_str_mv |
Vinhas, Raquel Lourenço, Alexandra Santos, Susana Lemos, Marcos Ribeiro, Patrícia de Sousa, Aida Botelho Baptista, Pedro Viana Fernandes, Alexandra Ramos |
| dc.subject.por.fl_str_mv |
ALL E14a2 Mutation P.Y440C Philadelphia chromosome Oncology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| topic |
ALL E14a2 Mutation P.Y440C Philadelphia chromosome Oncology Pharmacology (medical) SDG 3 - Good Health and Well-being |
| description |
cofinanced by the ERDF under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007728). Inn-INDIGO/0002/2015. |
| publishDate |
2018 |
| dc.date.none.fl_str_mv |
2018-01-01 2018-01-01T00:00:00Z 2021-11-15T23:29:27Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/127779 |
| url |
http://hdl.handle.net/10362/127779 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1178-6930 PURE: 10569353 https://doi.org/10.2147/OTT.S177019 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
10 application/pdf |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799138066238013440 |