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Tumores do tecido hematopoiético e linfático que afetam as células B maduras
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Os grandes progressos obtidos na identificação do genoma humano revolucionaram a forma como se abordam, atualmente, as patologias de foro oncológico (1).
O objetivo deste estudo foi estudar, ao nível do diagnóstico e da terapêutica, as neoplasias linfóides que afetam, principalmente, as células B maduras.
Neste trabalho, foi utilizada a última classificação dos tumores do tecido hematopoiético e linfático, da Organização Mundial de Saúde, publicada em 2016. Esta abordagem, baseada em múltiplos parâmetros, foi validada em inúmeros estudos e apresentada como sendo altamente reprodutível e de uso vantajoso na investigação clínica.
Atendendo a que, este tema, engloba numerosas entidades, foram desenvolvidas as mais relevantes, quer pela sua taxa de frequência, quer pelas suas particularidades clínicas. Nomeadamente, a leucemia linfocítica crónica, a leucemia a tricoleucocitos, o linfoma folicular, o linfoma difuso de grandes células B, o linfoma do manto, o linfoma de Burkitt, linfoma de Hodgkin e o mieloma múltiplo (2).
As técnicas de citometria de fluxo, têm sido o método preferencial para a determinação da linhagem celular e análise da maturação das células nas neoplasias hematológicas. Permitem detetar e quantificar antigénios celulares de superfície, citoplasmáticos e nucleares. Para identificar as alterações genéticas, técnicas de citogenética como a hibridação in situ por imunofluorescência, a cariotipagem espectral e a hibridação genómica comparativa, são utilizadas preferencialmente (3,4).
Neste trabalho, foram discutidas as terapias convencionais, confrontando-as com as estratégias terapêuticas emergentes. A disponibilidade de novos fármacos, mais específicos, aumentou significativamente a qualidade de vida e a sobrevivência dos doentes com neoplasias linfóides. Aos agentes quimioterápicos convencionais, foram adicionados fármacos específicos tais como: anticorpos monoclonais (rituximab), imunomoduladores (talidomida e lenalidomida), inibidores do proteossoma (bortezomib), inibidores da tirosina cinase de Bruton (ibrutinib) e inibidores da B cell lymphoma protein 2 (venetoclax), entre outros (5).
A investigação, no futuro, orientando-se para uma medicina de precisão, deve procurar identificar, com acuidade, as alterações genéticas responsáveis pelas diversas neoplasias linfóides e continuar a desenvolver estratégias terapêuticas cada vez mais específicas (5).
In recent years we have witnessed a substantial development in the identification of the human genome. This, led to a revolution on the approach of oncologic disorders and their therapeutics (1). The aim of this study is to characterize the current status of the lymphoyd neoplasms that affect mostly mature B cells. In this work was used the World Health Organization (WHO) classification of Tumors of hematopoietic and lymphatic tissue, updated in 2016. The multiparameter approach to classification, adopted by the World Health Organization, has been validated in international studies as being highly reproducible and enhancing the interpretation of clinical and translational studies. Among the numerous entities that fit into B cell mature lymphomas, we have selected eight taking into account its high frequency and/ or its clinical particularities. These are chronic lymphocytic leukemia, hairy cells leucemia,follicular lymphoma, large B cells diffuse lymphoma, mantle cells lymphoma, Burkitt’s lymphoma, multiple myeloma, and Hodgkin’s lymphoma (2). The flow citometry technics, has been the preferred method to determine cell lines and examine maturation process of neoplasic cells (3). To identify genetic transformations, citogenetic technics such as immunofluorescence in situ hybridization, spectral karyotyping and comparative genomic hybridization are used (4). The standard therapy, and the correlation with new specific drugs for each of this disorders was discussed. The availability of new specific drugs increased the lifespan of the pacients and improved their quality of life. To convencional chemmoterapic agents, better targeted drugs have been added, such as monoclonal antibodies (rituximab), immunomodulatory agents (thalidomide, lenalidomide), proteossom inhibitor (bortezomib), Bruton’s tirocinase inhibitor (ibrutinib), B cell lymphoma 2 protein inhibitor (venetoclax), among others (5). Future research, heading towards precision medicine, should seek to better identify each particular genetic alteration of lymphoid neoplasms and continue to improve increasingly specific therapeutic strategies (5).
In recent years we have witnessed a substantial development in the identification of the human genome. This, led to a revolution on the approach of oncologic disorders and their therapeutics (1). The aim of this study is to characterize the current status of the lymphoyd neoplasms that affect mostly mature B cells. In this work was used the World Health Organization (WHO) classification of Tumors of hematopoietic and lymphatic tissue, updated in 2016. The multiparameter approach to classification, adopted by the World Health Organization, has been validated in international studies as being highly reproducible and enhancing the interpretation of clinical and translational studies. Among the numerous entities that fit into B cell mature lymphomas, we have selected eight taking into account its high frequency and/ or its clinical particularities. These are chronic lymphocytic leukemia, hairy cells leucemia,follicular lymphoma, large B cells diffuse lymphoma, mantle cells lymphoma, Burkitt’s lymphoma, multiple myeloma, and Hodgkin’s lymphoma (2). The flow citometry technics, has been the preferred method to determine cell lines and examine maturation process of neoplasic cells (3). To identify genetic transformations, citogenetic technics such as immunofluorescence in situ hybridization, spectral karyotyping and comparative genomic hybridization are used (4). The standard therapy, and the correlation with new specific drugs for each of this disorders was discussed. The availability of new specific drugs increased the lifespan of the pacients and improved their quality of life. To convencional chemmoterapic agents, better targeted drugs have been added, such as monoclonal antibodies (rituximab), immunomodulatory agents (thalidomide, lenalidomide), proteossom inhibitor (bortezomib), Bruton’s tirocinase inhibitor (ibrutinib), B cell lymphoma 2 protein inhibitor (venetoclax), among others (5). Future research, heading towards precision medicine, should seek to better identify each particular genetic alteration of lymphoid neoplasms and continue to improve increasingly specific therapeutic strategies (5).
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2017
Palavras-chave
Diagnóstico Terapêutica Leucemia linfocítica crónica Linfoma folicular Linfoma difuso de grandes células B Leucemia por tricoleucócitos Linfoma do manto Linfoma de Burkitt Linfoma de Hodgkin Mieloma múltiplo Mestrado Integrado - 2017