MUTAÇÕES EM PML-RARA E RESISTÊNCIA AO ATRA NA LEUCEMIA PROMIELOCÍTICA AGUDA PEDIÁTRICA

Beatriz Mendes  Galvão; Monica Aparecida  Ganazza; Amilcar Cardoso De  Azevedo; José Andrés  Yunes

doi:10.51161/rems/2340

MUTAÇÕES EM PML-RARA E RESISTÊNCIA AO ATRA NA LEUCEMIA PROMIELOCÍTICA AGUDA PEDIÁTRICA

Autores

Beatriz Mendes Galvão
Monica Aparecida Ganazza
Amilcar Cardoso De Azevedo
José Andrés Yunes

DOI:

https://doi.org/10.51161/rems/2340

Palavras-chave:

LPA, MUTAÇÕES, PML-RARA

Resumo

Introdução: A leucemia promielocítica aguda (LPA) apresenta a translocação t(15;17) em 95% dos casos, envolvedo os genes PML (15q24.1) e RARA (17q21.2) e resulta na formação de um transcrito e proteína de fusão PML-RARA. O tratamento da LPA baseia-se no uso de ácido all-trans retinóico (ATRA) combinado à quimioterapia com antraciclina. Recentemente o trióxido de arsênico (ATO) foi incorporado ao tratamento, demonstrando melhora considerável do sucesso terapêutico. Porém, alguns pacientes ainda apresentam má resposta ou resistência ao tratamento e estudos sugerem que mutações no transcrito de fusão PML-RARA podem ser responsáveis por este comportamento. Acreditamos que, as mutações possam estar presentes no domínio Bbox do gene PML, responsável pela supressão de crescimento e apoptose das células e/ou no domínio LBD do gene RARA, responsável pela formação do complexo RARA/RXR que acarreta na ligação do ATRA às células leucêmicas. Objetivos: Portanto, o presente estudo tem como objetivo analisar e identificar mutações em PML-RARA em casos de LPA admitidos para tratamento no Centro Infantil Boldrini no período entre 2000 a 2020. Materiais e Métodos: Neste período, foram admitidos 121 pacientes pediátricos com LPA, positivos para a t(15;17), destes, 12 pacientes apresentaram recaída molecular e 3 apresentaram má resposta ao tratamento. Foi padronizada a reação de cadeia da polimerase (PCR) em duas etapas (Nested-PCR) para a amplificação do gene de fusão PML-RARA, utilizando iniciadores que cobrem do éxon 1 do PML ao éxon 7 de RARA, os amplicons da Nested-PCR foram sequenciados bidirecionalmente através do sequenciamento Sanger, utilizando iniciadores no domínio Bbox do gene PML e no domínio LBD de RARA e os cromatogramas gerados foram analisados por inspeção visual no software Chromas e a sequência em FASTA foi submetida para análises no Software MutationExplorer. Resultados: A partir disso, até o presente momento, 7 pacientes foram sequenciados, dos quais um recidivado, apresentou uma mutação no domínio LBD, sendo ela uma deleção de aproximadamente 600 pares de base. Conclusão: Desta forma, pode-se concluir até o presente momento, que aproximadamente 14% dos pacientes que apresentaram recaída molecular da LPA possuem mutações no domínio LBD. Até o final do estudo, todos os pacientes serão sequenciados e analisados para ambos os domínios.

Publicado

2021-11-08

Como Citar

Galvão, B. M. ., Ganazza, M. A. ., Azevedo, A. C. D. ., & Yunes, J. A. . (2021). MUTAÇÕES EM PML-RARA E RESISTÊNCIA AO ATRA NA LEUCEMIA PROMIELOCÍTICA AGUDA PEDIÁTRICA. Revista Multidisciplinar Em Saúde, 2(4), 26. https://doi.org/10.51161/rems/2340

Baixar Citação

Edição

v. 2 n. 4 (2021)

Seção

II Congresso Brasileiro de Biologia Molecular On-line

Licença

Este trabalho está licenciado sob uma licença Creative Commons Attribution 4.0 International License.

O conteúdo desta revista foi migrado para https://editoraintegrar.com.br

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Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
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Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
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Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
PKPApplication.execute() % line   68, file: index.php

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            PKPTemplateManager.display(frontend/pages/article.tpl) % line  292, file: ArticleHandler.inc.php
         ArticleHandler.view(Array[1], Object:Request) % line  391, file: PKPRouter.inc.php
      PKPRouter._authorizeInitializeAndCallRequest(Array[2], Object:Request, Array[1], false) % line  231, file: PKPPageRouter.inc.php
   PKPPageRouter.route(Object:Request) % line  143, file: Dispatcher.inc.php
Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
PKPApplication.execute() % line   68, file: index.php

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                                                         SubmissionSearch._getMergedPhraseResults(Object:Journal, Array[1], , null, null, 500, 1) % line  146, file: SubmissionSearch.inc.php
                                                      SubmissionSearch._getMergedKeywordResults(Object:Journal, Array[4], , null, null, 500, 1) % line  194, file: SubmissionSearch.inc.php
                                                   SubmissionSearch._getMergedPhraseResults(Object:Journal, Array[4], null, null, null, 500, 1) % line  146, file: SubmissionSearch.inc.php
                                                SubmissionSearch._getMergedKeywordResults(Object:Journal, Array[3], null, null, null, 500, 1) % line  132, file: SubmissionSearch.inc.php
                                             SubmissionSearch._getMergedArray(Object:Journal, Array[1], null, null) % line  263, file: SubmissionSearch.inc.php
                                          SubmissionSearch.retrieveResults(Object:Request, Object:Journal, Array[1], null, null, null, Object:DBResultRange, Array[1]) % line   92, file: RecommendBySimilarityPlugin.inc.php
                                       RecommendBySimilarityPlugin.callbackTemplateArticlePageFooter(Templates::Article::Footer::PageFooter, Array[3]) % line  107, file: HookRegistry.inc.php
                                    HookRegistry.call(Templates::Article::Footer::PageFooter, Array[3]) % line 1267, file: PKPTemplateManager.inc.php
                                 PKPTemplateManager.smartyCallHook(Array[1], Object:Smarty_Internal_Template) % line   43, file: 42362804174f266c598cdb32c3208fc745b92101^1c372c95cd85572e0fbc9a53d0323a0b229cfc78_0.app.frontendpagesarticle.tpl.php
                              content_6781613650b432_13896783(Object:Smarty_Internal_Template) % line  123, file: smarty_template_resource_base.php
                           Smarty_Template_Resource_Base.getRenderedTemplateCode(Object:Smarty_Internal_Template) % line  114, file: smarty_template_compiled.php
                        Smarty_Template_Compiled.render(Object:Smarty_Internal_Template) % line  216, file: smarty_internal_template.php
                     Smarty_Internal_Template.render(false, 1) % line  232, file: smarty_internal_templatebase.php
                  Smarty_Internal_TemplateBase._execute(Object:Smarty_Internal_Template, null, 42362804174f266c598cdb32c3208fc745b92101, null, 1) % line  134, file: smarty_internal_templatebase.php
               Smarty_Internal_TemplateBase.display(frontend/pages/article.tpl, null, 42362804174f266c598cdb32c3208fc745b92101, null) % line  924, file: PKPTemplateManager.inc.php
            PKPTemplateManager.display(frontend/pages/article.tpl) % line  292, file: ArticleHandler.inc.php
         ArticleHandler.view(Array[1], Object:Request) % line  391, file: PKPRouter.inc.php
      PKPRouter._authorizeInitializeAndCallRequest(Array[2], Object:Request, Array[1], false) % line  231, file: PKPPageRouter.inc.php
   PKPPageRouter.route(Object:Request) % line  143, file: Dispatcher.inc.php
Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
PKPApplication.execute() % line   68, file: index.php

                                                                  ADOConnection.CacheExecute(3600, SELECT 				o.submission_id, 				MAX(s.context_id) AS journal_id, 				MAX(i.date_published) AS i_pub, 				MAX(p.date_published) A..., Array[2]) % line  132, file: DAO.inc.php
                                                               DAO.retrieveCached(SELECT 				o.submission_id, 				MAX(s.context_id) AS journal_id, 				MAX(i.date_published) AS i_pub, 				MAX(p.date_published) A..., Array[2], 3600) % line   91, file: ArticleSearchDAO.inc.php
                                                            ArticleSearchDAO.getPhraseResults(Object:Journal, Array[1], null, null, , 500, 1) % line  201, file: SubmissionSearch.inc.php
                                                         SubmissionSearch._getMergedPhraseResults(Object:Journal, Array[1], , null, null, 500, 1) % line  146, file: SubmissionSearch.inc.php
                                                      SubmissionSearch._getMergedKeywordResults(Object:Journal, Array[4], , null, null, 500, 1) % line  194, file: SubmissionSearch.inc.php
                                                   SubmissionSearch._getMergedPhraseResults(Object:Journal, Array[4], null, null, null, 500, 1) % line  146, file: SubmissionSearch.inc.php
                                                SubmissionSearch._getMergedKeywordResults(Object:Journal, Array[3], null, null, null, 500, 1) % line  132, file: SubmissionSearch.inc.php
                                             SubmissionSearch._getMergedArray(Object:Journal, Array[1], null, null) % line  263, file: SubmissionSearch.inc.php
                                          SubmissionSearch.retrieveResults(Object:Request, Object:Journal, Array[1], null, null, null, Object:DBResultRange, Array[1]) % line   92, file: RecommendBySimilarityPlugin.inc.php
                                       RecommendBySimilarityPlugin.callbackTemplateArticlePageFooter(Templates::Article::Footer::PageFooter, Array[3]) % line  107, file: HookRegistry.inc.php
                                    HookRegistry.call(Templates::Article::Footer::PageFooter, Array[3]) % line 1267, file: PKPTemplateManager.inc.php
                                 PKPTemplateManager.smartyCallHook(Array[1], Object:Smarty_Internal_Template) % line   43, file: 42362804174f266c598cdb32c3208fc745b92101^1c372c95cd85572e0fbc9a53d0323a0b229cfc78_0.app.frontendpagesarticle.tpl.php
                              content_6781613650b432_13896783(Object:Smarty_Internal_Template) % line  123, file: smarty_template_resource_base.php
                           Smarty_Template_Resource_Base.getRenderedTemplateCode(Object:Smarty_Internal_Template) % line  114, file: smarty_template_compiled.php
                        Smarty_Template_Compiled.render(Object:Smarty_Internal_Template) % line  216, file: smarty_internal_template.php
                     Smarty_Internal_Template.render(false, 1) % line  232, file: smarty_internal_templatebase.php
                  Smarty_Internal_TemplateBase._execute(Object:Smarty_Internal_Template, null, 42362804174f266c598cdb32c3208fc745b92101, null, 1) % line  134, file: smarty_internal_templatebase.php
               Smarty_Internal_TemplateBase.display(frontend/pages/article.tpl, null, 42362804174f266c598cdb32c3208fc745b92101, null) % line  924, file: PKPTemplateManager.inc.php
            PKPTemplateManager.display(frontend/pages/article.tpl) % line  292, file: ArticleHandler.inc.php
         ArticleHandler.view(Array[1], Object:Request) % line  391, file: PKPRouter.inc.php
      PKPRouter._authorizeInitializeAndCallRequest(Array[2], Object:Request, Array[1], false) % line  231, file: PKPPageRouter.inc.php
   PKPPageRouter.route(Object:Request) % line  143, file: Dispatcher.inc.php
Dispatcher.dispatch(Object:Request) % line  281, file: PKPApplication.inc.php
PKPApplication.execute() % line   68, file: index.php

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