Navegando por Palavras-chave "Chronic Myeloid Leukemia"
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- ItemAcesso aberto (Open Access)Chronic myeloid leukemia (CML): prognostic factors and survival analysis(Associação Paulista de Medicina - APM, 1996-02-01) Colleoni, Gisele Wally Braga [UNIFESP]; Chauffaille, Maria de Lourdes Lopes Ferrari [UNIFESP]; Moncau, José Eduardo Cajado [UNIFESP]; Souto, Elizabeth Xisto [UNIFESP]; Silva, Maria Regina Regis [UNIFESP]; Kerbauy, José [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The prognostic value of different factors upon diagnosis of CML was analysed in 45 Philadelphia (Ph1)-positive patients. The median survival was 48 months. Univariate analysis showed 5 poor prognostic factors (male sex, under 45 years-old, bone marrow blasts greater than or equal to 10 percent, blood basophils greater than or equal to 6 percent and blood eosinophils greater than or equal to 6 percent) which provided for the development of a clinical staging system: Stage I with none or one factor and a two-year survival rate of 100 percent; Stage II with two or three factors and two-year survival of 72.2 percent; and Stage III with four or five factors and two-year survival of 0 percent (p = 0.00016). Multivariate survival analysis showed that combination of blood basophilia and bone marrow blasts had the strongest predictive relationship to survival time. We conclude that a combination of pretreatment factors identifies different risk subcategories in CML patients and is helpful in assessing the overall prognosis and the treatment approach.
- ItemAcesso aberto (Open Access)Correlação entre adesão ao tratamento e resposta molecular, falha no tratamento e sobrevida global na leucemia mielóide crônica: uma revisão de literatura(Universidade Federal de São Paulo, 2024-08-26) Vieira, Nathalya Melo; Silva, Antonio Távora de Albuquerque; http://lattes.cnpq.br/3661583782451650A Leucemia Mieloide Crônica (LMC) é uma neoplasia mieloproliferativa, provocada pela translocação entre os cromossomos 9 e 22, do qual origina-se o cromossomo Philadelphia (Ph). Essa doença hematológica apresenta três fases: crônica, acelerada (ou transformação) e crise blástica. Atualmente, a LMC é tratada por meio de medicamentos (inibidores de tirosina quinase, ITK) via oral, como: imatinibe, nilotinibe e dasatinibe, o qual exige do paciente a adesão a terapia. E em virtude da importância da adesão ao tratamento oral para essa neoplasia, este trabalho de revisão de literatura teve como objetivo: verificar se existe correlação entre a adesão e/ou a falta de adesão ao tratamento (com imatinibe e/ou nilotinibe e/ou dasatinibe) em pacientes adultos com Leucemia Mieloide Crônica (LMC) e os seguintes desfechos: sobrevida global e/ou resposta molecular e/ou falha no tratamento. Para isso, foi elaborada uma pergunta de pesquisa e montada uma estratégia de busca, a qual foi aplicada na base de dados PubMed, respeitando-se também critérios de exclusão estabelecidos para este estudo. Tal metodologia resultou na inclusão de 5 artigos para análise neste estudo de revisão, dos quais: a) todos possuem desenho observacional, com destaque para 3 trabalhos de coorte; b) o estudo com menor amostra contêm 38 pacientes e o com maior amostra possuí 300 pessoas; c) os ITK que mais apareceram nos estudos foram imatinibe e nilotinibe; d) os métodos mais empregados para verificar a adesão foram a Escala de Adesão à Medicação de Morisky (MMAS) e contagem de comprimidos; e) sobre os desfechos de interesse, o desfecho “sobrevida global” não foi encontrado em nenhum artigo incluído neste estudo, o desfecho “falha no tratamento” foi identificado em apenas um artigo, e a “Resposta Molecular” (RM) foi encontrada em todos os 5 artigos incluídos nesta revisão; e f) 3 estudos citam existir correlação entre adesão ao tratamento com ITK e o desfecho RM. Contudo, somente 1 desses 3 trabalhos apresentou medida de associação entre a adesão do paciente ao tratamento com os ITK e a RM. Portanto, com os resultados obtidos neste trabalho, foi possível verificar a existência de correlação entre a adesão ao tratamento com os ITK de interesse em pacientes adultos com LMC e o desfecho “Resposta Molecular”, evidenciando a importância da verificação da adesão ao tratamento oral com ITK, durante o acompanhamento de pacientes adultos com LMC e da Resposta Molecular.
- ItemAcesso aberto (Open Access)Leucemia Mielóide Crônica em pediatria: perspectivas atuais(Associação Brasileira de Hematologia e Hemoterapia e Terapia Celular, 2008-04-01) Lee, Maria Lúcia de Martino [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Chronic myeloid leukemia (CML) is a rare event in childhood, comprising of less than 5% of all leukemia cases in this age group. CML is characterized by the presence of a specific molecular marker, the Ph+ chromosome, which is responsible for almost all etiopathogenesis, hence, it has clinical and course characteristics that do not differ from the adult population. In pediatrics the therapeutic approach is based mainly on the experience obtained with adult protocols. With bone marrow transplantation (BMT) being the only cure option, this procedure is more effective in patients with compatible related donors and performed during the initial chronic phase of the disease. The great anti-leukemic efficacy seen with imatinib mesylate was responsible for the approval of this drug in pediatric use for intolerant or refractory -interferon treated patients or relapsed patients after BMT. Currently, its use in pediatric patients with recently diagnosed CML, who have a compatible donor, has become a great dilemma. There is no agreement yet on which is the best way to use this drug or even whether it will ever replace BMT. Further studies with longer follow-up periods are still needed.
- ItemSomente MetadadadosModulação do eixo PLCγ1, Ca2+/CAMKII e PKC em células de leucemia mieloide crônica tratadas com violaceína(Universidade Federal de São Paulo (UNIFESP), 2020-07-30) Miura, Natalia Tamagusko [UNIFESP]; Justo, Giselle Zenker [UNIFESP]; Universidade Federal de São PauloViolacein is an indole derivative isolated from Chromobacterium violaceum with potential antitumor activity and specific mechanisms of action in vitro and in vivo. This compound was evaluated in vitro in cultures of chronic myeloid leukemia (CML), which is a myeloproliferative disease associated with a genetic translocation that leads to the formation of the BCR-ABL oncoprotein. BCR-ABL is capable of inducing multiple signal transduction pathways responsible for the leukemogenic process. Moreover, BCR-ABL acts with additional mechanisms, dependent or independent of BCR-ABL, to induce resistance, leading to an unfavorable prognosis in the treatment of the disease and the search for alternative drug therapies. One of the factors that lead to the phenotype of multiple drug resistance (MDR) is related to the increase in the expression of efflux pumps, among them, the P glycoproteins (Pgp), which is one of the most studied mechanisms of chemoresistance in CML. Hence, we compared the phosphoproteomic profile of K562 cells and their variant that overexpresses the Pgp and, therefore, presents the MDR phenotype, the Lucena 1 cell line, using a microarray approach of peptides that allows to analyze the activity of different cell kinases. Data analysis showed that the exposure of K562 cells to violacein significantly modulated 13 kinases, whereas the activity of 6 kinases in Lucena 1 cells showed significant changes after treatment. The results showed a reduction in the activity of Axl and c-Met in K562 cells, while p38MAPK and JNK stimulation were observed in Lucena 1 cells. Of particular importance, the quinoma analysis indicated significant modulation in protein kinase C (PKC) activity after treatment of cells of both strains with violacein. In this sense, a reduction in phosphorylation of PKCα(Ser657) by immunoblotting was also observed. On the other hand, the pretreatment of cells with the specific classic PKC inhibitor, chelerythrine, inhibited about 80% of cell death induced by violacein, corroborating the increase in intracellular Ca2+ concentration. In addition, a significant increase in CAMKII(Thr286) activity was observed, suggesting that stimulation of the Ca2+/CAMKII axis and PKCs is important for cell death induced by violacein. In addition, the results also demonstrated the inhibition of PLCγ1(Tyr783), suggesting that this effect is also involved in inducing cell death. Together, the results indicate an important role for Ca2+ signaling and PLCγ1 inhibition in violacein-induced CML cell death. They also open perspectives for investigating new targets of action of this naturally derived compound.
- ItemSomente MetadadadosPerfil proteolítico de células de leucemia mielóide crônica(Universidade Federal de São Paulo (UNIFESP), 2020-07-30) Amador, Fernanda Cardoso [UNIFESP]; Juliano, Maria Aparecida [UNIFESP]; Universidade Federal de São PauloObjective: Identification and differentiation of protease classes present in Chronic Myeloid Leukemia cells (K562 and Lucena 1) by studying the interference of pH and variation of enzymatic substrates on their proteolytic activities; comparison of intracellular proteases of the two cell lines by peptidomi analysis; in silico data processing for protease mapping. Methods: Lyses of the two cell lines studied and substrate variation and pH analysis were performed in fluorescence studies by substrate hydrolysis, chromatographic peptide analysis and mass spectrometry and in silico data treatment for protease mapping. Results: It was possible to identify through the tests performed the classes of proteases present in the two cell lines and differentiate them. Most proteases found in both lines are similar, corroborating that Lucena 1 cells are similar to K562 cells – both Chronic Myeloid Leukemia cell lines - containing only the difference in the development of Lucena 1 Multiple Drug Resistance. However, the presence of protease Suppressor of tumorigenicity 14 protein (EC: 3.4.21.109) only in Lucena 1 cells concludes the difference sought in this research. Conclusions: The protease in question has been described as an adjunct in the development of Multiple Drug Resistance in Chronic Myeloid Leukemia cells treated with doxorubicin chemotherapy. The identification of this proteolytic enzyme is fundamental for the development of future treatment methods, considering that the drugs for the cure of leukemia are mostly functional, having as a misfortune the tumor cells perspicacity to develop resistance to chemotherapy.