A carregar...
Publicação
Mielofibrose secundária a trombocitemia essencial : caso clínico e revisão bibliográfica
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 780.65 KB | Adobe PDF |
Autores
Orientador(es)
Resumo(s)
As doenças mieloproliferativas constituem um grupo heterogéneo de patologias, com origem numa célula progenitora hematopoiética multipotente. A classificação da Organização Mundial de Saúde inclui oito doenças mieloproliferativas crónicas: Leucemia mielóide crónica, Leucemia neutrofílica crónica, Leucemia eosinofílica crónica não especificada, Mastocitose sistémica, Policitemia vera, Mielofibrose primária, Trombocitemia essencial e Neoplasias mieloproliferativas, não classificáveis. Nesta classificação há uma extensa heterogeneidade fenotípica com base genética, ainda que algumas patologias estejam ainda muito pouco caracterizadas. Na verdade, a mieloproliferação anormal justifica-se pela activação constitucional de vias de transdução de sinais, causadas por rearranjos genéticos ou mutações que afectam as proteínas tirosina cinases ou moléculas relacionadas. Nos últimos anos, foram descritas novas mutações nos genes MPL e JAK2, que permitiram ampliar o conhecimento sobre as bases moleculares destas doenças e deste modo, aperfeiçoar a sua capacidade de diagnóstico e tratamento. Estas descobertas resultaram no desenvolvimento de terapêutica molecular dirigida, nomeadamente os inibidores JAK2. Estes fármacos têm sido efectivos no controlo da hiperproliferação de células hematopoiéticas e no alívio dos sintomas constitucionais. Os ensaios clínicos a decorrer permitirão uma melhor avaliação sobre os benefícios e segurança destes compostos. Neste trabalho é apresentado o caso clínico de uma mulher de 55 anos com diagnóstico inicial de Trombocitémia Essencial que evoluiu para Mielofibrose e com actual tranformação leucémica. Assim, a partir do caso descrito pretende-se rever o diagnóstico e curso clínico das neoplasias mieloproliferativas BCR-ABL negativas, com destaque para a mielofibrose, assim como as opções terapêuticas actuais em estudo, incluindo os recentes inibidores da JAK.
The myeloproliferative disorders constitute an heterogeneous group of diseases, which share an origin in a multipotent hematopoietic progenitor cell. The World Health Organization of the myeloproliferative neoplasms includes eight disorders: Chronic mieloide leukemia, Chronic neutrophilic leukemia, Chronic eosinophilic leukemia, Polycythemia vera, Primary myelofibrosis, Essential thrombocytosis, Sistemic mastocytosis, Myeloprolferative neoplasms, unclassifiable. Within this broad classification, exists a significant phenotypic heterogeneity, and still there is some disorders rare or poorly characterized. Indeed the abnormal proliferation it’s explained by the constitutional activation of signal transductional pathways, where genetic rearrangements and mutations afectting tirosine-cinase proteins or relationed molecules where described. In recent years, were identified new mutations in genes MPL and JAK2, which allowed further knowledge from molecular basis and even were able to sublime the diagnostic and treatment techniques. This new chapter, triggered development of molecular targeted therapies, particulary JAK2 inihibitors. These agents, have been effective in controlling hyperproliferative hematopoetic stem cells and in relieving constitucional symptoms. Currently ongoing clinical trials will be able to give a better evaluation about drugs bennefits and safety. In this work, is presented a case study of a 55-year-old woman with the initial diagnosis of Essential trombocytemia, wich evolved to myelofibrosis, and recently has presented criteria to leukemic transformation. Finally, this work intends to review the diagnosis and clinical course of myeloproliferative neoplasms, outstanding Myelofibrosis, as well as the current terapies in study, including the newcomers JAK inhibitors.
The myeloproliferative disorders constitute an heterogeneous group of diseases, which share an origin in a multipotent hematopoietic progenitor cell. The World Health Organization of the myeloproliferative neoplasms includes eight disorders: Chronic mieloide leukemia, Chronic neutrophilic leukemia, Chronic eosinophilic leukemia, Polycythemia vera, Primary myelofibrosis, Essential thrombocytosis, Sistemic mastocytosis, Myeloprolferative neoplasms, unclassifiable. Within this broad classification, exists a significant phenotypic heterogeneity, and still there is some disorders rare or poorly characterized. Indeed the abnormal proliferation it’s explained by the constitutional activation of signal transductional pathways, where genetic rearrangements and mutations afectting tirosine-cinase proteins or relationed molecules where described. In recent years, were identified new mutations in genes MPL and JAK2, which allowed further knowledge from molecular basis and even were able to sublime the diagnostic and treatment techniques. This new chapter, triggered development of molecular targeted therapies, particulary JAK2 inihibitors. These agents, have been effective in controlling hyperproliferative hematopoetic stem cells and in relieving constitucional symptoms. Currently ongoing clinical trials will be able to give a better evaluation about drugs bennefits and safety. In this work, is presented a case study of a 55-year-old woman with the initial diagnosis of Essential trombocytemia, wich evolved to myelofibrosis, and recently has presented criteria to leukemic transformation. Finally, this work intends to review the diagnosis and clinical course of myeloproliferative neoplasms, outstanding Myelofibrosis, as well as the current terapies in study, including the newcomers JAK inhibitors.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016
Palavras-chave
Mielofibrose secundária Trombocitemia essencial