Resumo Introdução: A tuberculose (TB) é uma possível complicação grave do transplante de órgãos sólidos, associada à alta mortalidade e morbidade. A TB pós-transplante tem patogênese variada com muitas abordagens para sua prevenção, que é a forma mais importante de reduzir sua incidência. O tratamento da TB em receptores de órgãos é um desafio devido à toxicidade dos medicamentos e à interação com imunossupressores. Relato de caso: uma mulher de 18 anos que foi submetida a transplante renal de um doador falecido e recebeu alta com função renal adequada foi readmitida no 37º dia de pós-operatório com febre. A TC mostrou sinais de TB miliar e coleção de fluidos além de fistulização do enxerto através da pele. A paciente apresentou BAAR positivo no fluido drenado e bacilo de Koch na urina. Ela foi tratada com um esquema de quatro medicamentos (rifampicina, isoniazida, pirazinamida e etambutol), com ótima resposta e função de enxerto preservada. Fomos informados de que o receptor do rim contralateral também apresentou TB pós-transplante, implicando em uma origem derivada do doador. Conclusão: A TB é um importante diagnóstico diferencial para complicações infecciosas em pacientes após transplante de órgãos sólidos, especialmente em regiões endêmicas. Sua apresentação clínica inicial pode não ser específica e deve ser suspeitada na presença de febre ou formação de coleções de fluidos. A suspeita de TB é a chave para o diagnóstico precoce e desfechos satisfatórios na TB pós-transplante.

Abstract Introduction: Tuberculosis (TB) is a possible serious complication of solid organ transplantation, associated with high mortality and morbidity. Post-transplant TB has varied pathogenesis with many approaches to its prevention, which is the most important way to reduce its incidence. Treatment of TB in organ recipients is challenging because of drug toxicity and interaction with immunosuppressants. Case report: an 18-year-old woman that underwent kidney transplantation from a deceased donor and was discharged with fair renal function was readmitted at 37th postoperative day with fever. CT showed signs of miliary TB and fluid collection besides graft fistulization through the skin. The patient presented positive BAAR in the drained fluid and Koch's bacillus in the urine. She was treated with a four-drug regimen (rifampicin, isoniazid, pyrazinamide, and etambutol), with great response and preserved graft function. We were informed that the recipient of the contralateral kidney also presented post-transplant TB, implying in a donor-derived origin. Conclusion: TB is an important differential diagnosis for infectious complications in patients after solid-organ transplantation, especially in endemic regions. Its initial clinical presentation can be unspecific and it should be suspected in the presence of fever or formation of fluid collections. The suspicion of TB is the key to early diagnosis and satisfactory outcomes in post-transplant TB.

Abstract Background: Resistance to apoptosis in chronic myeloid leukemia (CML) is associated with constitutive tyrosine kinase activity of the Bcr-Abl oncoprotein. The deregulated expression of apoptosis-related genes and alteration in epigenetic machinery may also contribute to apoptosis resistance in CML. Tyrosine kinase inhibitors target the Bcr-Abl oncoprotein and are used in CML treatment. The resistance of CML patients to tyrosine kinase inhibitors has guided the search for new compounds that may induce apoptosis in Bcr-Abl+ leukemic cells and improve the disease treatment. Methods: In the present study, we investigated whether the L-amino acid oxidase isolated from Bothrops moojeni snake venom (BmooLAAO-I) (i) was cytotoxic to Bcr-Abl+ cell lines (HL-60.Bcr-Abl, K562-S, and K562-R), HL-60 (acute promyelocytic leukemia) cells, the non-tumor cell line HEK-293, and peripheral blood mononuclear cells (PBMC); and (ii) affected epigenetic mechanisms, including DNA methylation and microRNAs expression in vitro. Results: BmooLAAO-I induced ROS production, apoptosis, and differential DNA methylation pattern of regulatory apoptosis genes. The toxin upregulated expression of the pro-apoptotic genes BID and FADD and downregulated DFFA expression in leukemic cell lines, as well as increased miR-16 expression - whose major predicted target is the anti-apoptotic gene BCL2 - in Bcr-Abl+ cells. Conclusion: BmooLAAO-I exerts selective antitumor action mediated by H2O2 release and induces apoptosis, and alterations in epigenetic mechanisms. These results support future investigations on the effect of BmooLAAO-I on in vivo models to determine its potential in CML therapy.

ABSTRACT Background: Breast cancer is the neoplasm with both the highest incidence and mortality rate among women worldwide. Given the known snake venom cytotoxicity towards several tumor types, we evaluated the effects of BthTX-I from Bothrops jararacussu on MCF7, SKBR3, and MDAMB231 breast cancer cell lines. Methods: BthTX-I cytotoxicity was determined via MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide assay. Cell death was measured by a hypotonic fluorescent solution method, annexin-V-FITC/propidium iodide staining and by apoptotic/autophagic protein expression. Cancer stem cells (CSCs) were quantified by flow cytometry using anti-CD24-FITC and anti-CD44-APC antibodies and propidium iodide. Results: BthTX-I at 102 µg/mL induced cell death in all cell lines. The toxin induced apoptosis in MCF7, SKBR3, and MDAMB231 in a dose-dependent manner, as confirmed by the increasing number of hypodiploid nuclei. Expression of pro-caspase 3, pro-caspase 8 and Beclin-1 proteins were increased, while the level of the antiapoptotic protein Bcl-2 was diminished in MCF7 cells. BthTX-I changed the staining pattern of CSCs in MDAMB231 cells by increasing expression of CD24 receptors, which mediated cell death. Conclusions: BthTX-I induces apoptosis and autophagy in all breast cancer cell lines tested and also reduces CSCs subpopulation, which makes it a promising therapeutic alternative for breast cancer.

ABSTRACT Background: Cytokines are key immune mediators in physiological and disease processes, whose increased levels have been associated with the physiopathology of hematopoietic malignancies, such as myeloproliferative neoplasms. Methods: This study examined the plasma cytokine profiles of patients with essential thrombocythemia, primary myelofibrosis, polycythemia vera and of healthy subjects, and analyzed correlations with JAK2 V617F status and clinical-hematological parameters. Results: The proinflammatory cytokine levels were increased in myeloproliferative neoplasm patients, and the presence of the JAK2 V617F mutation was associated with high IP-10 levels in primary myelofibrosis patients. Conclusions: Essential thrombocythemia, primary myelofibrosis, and polycythemia vera patients exhibited different patterns of cytokine production, as revealed by cytokine network correlations. Together, these findings suggest that augmented cytokine levels are associated with the physiopathology of myeloproliferative neoplasms.

Abstract Background: Chronic myeloid leukemia (CML) is a BCR-ABL1+ myeloproliferative neoplasm marked by increased myeloproliferation and presence of leukemic cells resistant to apoptosis. The current first-line therapy for CML is administration of the tyrosine kinase inhibitors imatinib mesylate, dasatinib or nilotinib. Although effective to treat CML, some patients have become resistant to this therapy, leading to disease progression and death. Thus, the discovery of new compounds to improve CML therapy is still challenging. Here we addressed whether MjTX-I, a phospholipase A2 isolated from Bothrops moojeni snake venom, affects the viability of imatinib mesylate-resistant Bcr-Abl+ cell lines. Methods: We examined the cytotoxic and pro-apoptotic effect of MjTX-I in K562-S and K562-R Bcr-Abl+ cells and in the non-tumor HEK-293 cell line and peripheral blood mononuclear cells, using the 3-(4,5-dimethylthiazol-2-yl) −2,5-diphenyltetrazolium bromide and the hypotonic fluorescent solution methods, associated with detection of caspases 3, 8, and 9 activation and poly (ADP-ribose) polymerase (PARP) cleavage. We also analyzed the MjTX-I potential to modulate the expression of apoptosis-related genes in K562-S and K562-R cells. Results: MjTX-I decreased the viability of K562-S and K562-R cells by 60 to 65%, without affecting the viability of the non-tumor cells, i.e. it exerted selective cytotoxicity towards Bcr-Abl+ cell lines. In leukemic cell lines, the toxin induced apoptosis, activated caspases 3, 8, and 9, cleaved PARP, downregulated expression of the anti-apoptotic gene BCL-2, and upregulated expression of the pro-apoptotic gene BAD. Conclusion: The antitumor effect of MjTX-I is associated with its potential to induce apoptosis and cytotoxicity in Bcr-Abl positive cell lines sensitive and resistant to imatinib mesylate, indicating that MjTX-I is a promising candidate drug to upgrade the CML therapy.

ABSTRACT BACKGROUND: Myeloproliferative neoplasms are Philadelphia chromosome-negative diseases characterized by hyperproliferation of mature myeloid cells, associated or not with the Janus kinase 2 tyrosine kinase mutation, JAK2V617F. As there is no curative therapy, researchers have been investigating new drugs to treat myeloproliferative neoplasms, including l-amino acid oxidase from Calloselasma rhodostoma snake venom (CR-LAAO), which is a toxin capable of eliciting apoptosis in several tumor cell lines. OBJECTIVE: To evaluate the effects of l-amino acid oxidase from C. rhodostoma snake venom in the apoptotic machinery of JAK2-mutated cell lines. METHODS: The HEL 92.1.7 and SET-2 cell lines were cultured with l-amino acid oxidase and catalase for 12 h at 37 °C in 5% carbon dioxide. The cell viability was assessed by the multi-table tournament method, the level of apoptosis was measured by flow cytometry, and the expression of cysteine-dependent aspartate-specific proteases and cleaved Poly(ADP-ribose) polymerase were analyzed by Western blotting. RESULTS: l-Amino acid oxidase from C. rhodostoma snake venom was cytotoxic to HEL 92.1.7 and SET-2 cells (50% inhibitory concentration = 0.15 µg/mL and 1.5 µg/mL, respectively) and induced apoptosis in a concentration-dependent manner. Cell treatment with catalase mitigated the l-amino acid oxidase toxicity, indicating that hydrogen peroxide is a key component of its cytotoxic effect.The activated caspases 3 and 8 expression and cleaved PARP in HEL 92.1.7 and SET-2 cells confirmed the apoptosis activation by CR-LAAO. CONCLUSIONS: l-Amino acid oxidase from C. rhodostoma snake venom is a potential antineoplastic agent against HEL 92.1.7 and SET-2 JAK2V617F-positive cells as it activates the extrinsic apoptosis pathway.

Background Activation of the complement system plays an important role in the regulation of immune and inflammatory reactions, and contributes to inflammatory responses triggered by envenomation provoked byBothrops snakes. The present study aimed to assess whether Bothrops jararacussuand Bothrops pirajai crude venoms and their isolated toxins, namely serine protease (BjussuSP-I) and L-amino acid oxidase (BpirLAAO-I), modulate human complement system pathways.Methods Lyophilized venom and toxin samples solubilized in phosphate buffered saline were diluted in appropriate buffers to evaluate their hemolytic activity on the alternative and classical pathways of the complement system. Venom- and toxin-treated normal human serum was added to the erythrocyte suspension, and the kinetic of hemolysis was measured spectrophotometrically at 700 nm. The kinetic 96-well microassay format was used for this purpose. We determined the t ½values (time required to lyse 50 % of target erythrocytes), which were employed to calculate the percentage of inhibition of the hemolytic activity promoted by each sample concentration. To confirm complement system activation, complement-dependent human neutrophil migration was examined using the Boyden chamber model.Results At the highest concentration tested (120 μg/mL), B. jararacussu and B. pirajai crude venoms inhibited the hemolytic activity of the classical pathway (65.3 % and 72.4 %, respectively) more strongly than they suppressed the hemolytic activity of the alternative pathway (14.2 and 13.6 %, respectively). BjussuSP-I (20 μg/mL) did not affect the hemolytic activity of the classical pathway, but slightly decreased the hemolytic activity of the alternative pathway (13.4 %). BpirLAAO-I (50 μg/mL) inhibited 24.3 and 12.4 % of the hemolytic activity of the classical and alternative pathways, respectively. Normal human serum treated with B. jararacussu and B. pirajai crude venoms induced human neutrophil migration at a level similar to that induced by zymosan-activated normal human serum.Conclusion Together, the results of the kinetics of hemolysis and the neutrophil chemotaxis assay suggest that pre-activation of the complement system byB. jararacussu and B. pirajai crude venoms consumes complement components and generates the chemotactic factors C3a and C5a. The kinetic microassay described herein is useful to assess the effect of venoms and toxins on the hemolytic activity of the complement system.

The L-amino acid oxidases (LAAOs) constitute a major component of snake venoms and have been widely studied due to their widespread presence and various effects, such as apoptosis induction, cytotoxicity, induction and/or inhibition of platelet aggregation, hemorrhage, hemolysis, edema, as well as antimicrobial, antiparasitic and anti-HIV activities. The isolated and characterized snake venom LAAOs have become important research targets due to their potential biotechnological applications in pursuit for new drugs of interest in the scientific and medical fields. The current study discusses the antitumor effects of snake venom LAAOs described in the literature to date, highlighting the mechanisms of apoptosis induction proposed for this class of proteins.

As neoplasias mieloproliferativas crônicas cromossomo Filadélfia negativas são doenças hematológicas clonais que se caracterizam pela independência ou pela hipersensibilidade dos progenitores hematopoiéticos às citocinas. Os mecanismos celulares e moleculares envolvidos na fisiopatologia das neoplasias mieloproliferativas crônicas ainda não estão totalmente esclarecidos. Achados fisiopatológicos relevantes para as neoplasias mieloproliferativas crônicas estão associados às alterações genéticas como, por exemplo, a mutação somática no gene que codifica o JAK2 (JAK2V617F). A desregulação do processo de morte celular programada, denominada apoptose, parece participar da patogênese dessas desordens. Sabe-se que a desregulação da expressão dos genes pró- e antiapoptóticos promove a resistência das células à apoptose, culminando com o acúmulo das células mieloides e estabelecendo a neoplasia. Esta revisão enfocou as alterações na regulação da apoptose em neoplasias mieloproliferativas crônicas e a importância da melhor compreensão desse mecanismo para o desenvolvimento de novas terapias para essas doenças.

Philadelphia-chromosome negative chronic myeloproliferative neoplasms are clonal hematologic diseases characterized by hematopoietic progenitor independence from or hypersensitivity to cytokines. The cellular and molecular mechanisms involved in the pathophysiology of myeloproliferative neoplasms have not yet been fully clarified. Pathophysiologic findings relevant for myeloproliferative neoplasms are associated with genetic alterations, such as, somatic mutation in the gene that codifies JAK-2 (JAK V617F). Deregulation of the process of programmed cellular death, called apoptosis, seems to participate in the pathogenesis of these disorders. It is known that expression deregulation of pro- and anti-apoptotic genes promotes cell resistance to apoptosis, culminating with the accumulation of myeloid cells and establishing neoplasms. This review will focus on the alterations in apoptosis regulation in myeloproliferative neoplasms, and the importance of a better understanding of this mechanism for the development of new therapies for these diseases.

The retrovirus human T lymphotropic virus type 1 (HTLV-1) promotes spastic paraparesis, adult T cell leukaemia and other diseases. Recently, some human microRNAs (miRNAs) have been described as important factors in host-virus interactions. This study compared miRNA expression in control individuals, asymptomatic HTLV-1 carriers and HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis patients. The proviral load and Tax protein expression were measured in order to characterize the patients. hsa-miR-125b expression was significantly higher in patients than in controls (p = 0.0285) or in the HAM group (p = 0.0312). Therefore, our findings suggest that miR-125b expression can be used to elucidate the mechanisms of viral replication and pathogenic processes.

A desregulação da apoptose parece participar da fisiopatologia da policitemia vera (PV). Este estudo avaliou a expressão das moléculas da família Bcl-2 em células hematopoéticas CD34 + e leucócitos de 12 pacientes com PV. Foram realizados: a quantificação da expressão gênica por PCR em tempo real utilizando kit Sybrgreen Quantitect, avaliação da expressão de proteínas por western-blot e detecção da mutação JAK2 V617F segundo Baxter et al. (2005). Células CD34 + dos pacientes com PV apresentaram maior expressão de A1 e Mcl-1 (mediana: 22,6 e 5,2, respectivamente) em comparação com controles (0,9 e 0,5, p = 0,004 e p = 0,020) e expressão de Bcl-2 e Bcl-xL diminuída nestes pacientes (0,18 e 1,19) em relação aos controles (1,39 e 2,01, p = 0,006 e p = 0,020). Células CD34 + dos pacientes com PV mostraram expressão elevada de bid (14,4) em comparação aos controles (1,0; p = 0,002). Leucócitos dos pacientes mostraram aumento de A1 (7,41, p = 0,001) e expressão reduzida do Bax (0,19; p = 0,04) e Bad (0,2; p = 0,030). Não houve correlação entre percentagem de alelos JAK2 V617F mutados e expressão molecular. Pacientes com PV apresentaram alterações na expressão de moléculas Bcl-2 que podem interferir no controle da apoptose e contribuir para a patogênese da doença.

Apoptosis deregulation might have a role in the pathophysiology of polycythemia vera (PV). This study evaluated Bcl-2 molecule expression in CD34+ cells and leukocytes in 12 PV patients. Gene expression was investigated by real time PCR using SybrGreen Quantitect kit and protein expression was evaluated by western-blotting. JAK2 V617F mutation was detected according to Baxter et al (2005). CD34+ cells from PV patients presented higher levels of A1 and Mcl-1 expression (median: 22.6 and 5.2, respectively) in comparison with controls (0.9 and 0.5, p=0.004 and p=0.020); while Bcl-2 and Bcl-xL expression decreased in PV patients (0.18 and 1.19) compared with controls (1.39 and 2.01, p=0.006 and p=0.020). CD34+ cells in PV patients showed an elevated Bid expression (14.4) in comparison with healthy subjects (1.0; p=0.002). Patients' leukocytes showed an A1 augmentation (7.41, p=0.001) and a reduced expression of Bax (0.19; p=0.040) and Bad (0.2; p=0.030). There was no correlation between JAK2 V617F allele burden and molecular expression. PV patients showed alterations in Bcl-2 members' expression, which may interfere with control of apoptotic machinery and contribute to disease pathogenesis.

O objetivo do estudo foi comparar os parâmetros antropométricos e perfil glicêmico de idosos diabéticos tipo 2 praticantes de atividade física regular e não praticantes. MÉTODOS: O estudo, do tipo transversal, envolveu 70 idosos com diabetes mellitus tipo 2, com idade entre 60 e 80 anos. A coleta de dados foi através de questionário estruturado abordando: a) características demográficas dos pacientes (idade e nível de escolaridade) e b) características do padrão de atividade física (frequência, duração (min) e tempo (meses) da prática de exercícios físicos). Foram realizadas medidas antropométricas e verificação do perfil glicêmico (glico-hemoglobina). Os dados foram analisados no programa STATA versão 9.0. Foram calculados a média e desvio padrão da média (DP) e realizado o teste de análise de variância (ANOVA). Para verificar a associação de variáveis qualitativas, utilizou-se o teste exato de Fisher e as associações entre as variáveis quantitativas foram estimadas através do coeficiente de correlação de Pearson, com uma confiança de 95%. O nível de significância foi de p<0,05. RESULTADOS: Em relação ao nível de escolaridade, não houve influência na realização da prática de atividade física. Nos PAF observa-se uma diminuição do IMC e do perfil glicêmico, quando comparados aos NPAF. A caminhada foi a atividade física mais realizada pelos idosos (51,5%). A partir dos resultados obtidos na análise dos dados, foi possível mostrar os benefícios que a atividade física proporciona aos indivíduos no processo de envelhecimento e no bom controle glicêmico.

This study aimed to compare the anthropometric parameters and plasma glucose in elderly with type 2 diabetes who practice regular physical activity or not. METHODS: The cross-sectional study comprised 70 elderly people with type 2 diabetes mellitus (DM2), aged between 60 and 80 years. Data collection was through a structured questionnaire: a) demographic characteristics of patients (age and level of schooling) and b) characteristics of the pattern of physical activity (frequency, duration (min) and time (months) the practice of physical exercise). Anthropometric measurements were taken and verification of plasma glucose (glyco-hemoglobin). The data were analyzed in the program STATA version 9.0. The data was analyzed using mean and standard deviation of the mean (SD), and analysis of variance (ANOVA); to determine the combination of qualitative variables, it was used the Fisher exact test and associations between quantitative variables were estimated by the coefficient of Pearson's correlation, with 95% confidence. The level of significance was p<0.05. RESULTS: Concerning education level, there was no influence on the attainment of physical activity. In PAF there is a decrease of IMC and plasma glucose as compared to NPAF. The walk was the most physical activity undertaken by the elderly (51.5%). The results obtained in the analysis of data made it possible to show the benefits that physical activity gives individuals in the aging process and in good glycemic control.

Pantoea agglomerans is a Gram-negative bacterium whose isolates can be found in blood cultures and other secretions. This article described one outbreak of sepsis due to this bacterium in the pediatric urgent care center of a tertiary hospital, in Brasilia, Federal District. This was a case-control study and it evaluated the risk factors for acquisition of nosocomial sepsis caused by Pantoea agglomerans. Six case-patients and 15 control-patients have been found. The risk factors were: vomiting in the internment and presence of solution compositions in the intravenous hydration therapy received in bigger number than 2 compositions. The transference tube used for the compositions was contaminated with Pantoea agglomerans, characterizing the outbreak with common source. The evolution of all the patients was favorable.

INTRODUÇÃO: Na identificação de cepas de Salmonella, os métodos de sorotipagem e ribotipagem na detecção de marcadores epidemiológicos são os mais utilizados nos laboratórios de referência mundiais. Esses métodos moleculares são imprescindíveis na vigilância epidemiológica e permitem a detecção da fonte da infecção. OBJETIVOS: O presente trabalho objetivou caracterizar as cepas de Salmonella Enteritidis pela ribotipagem. MATERIAL E MÉTODOS: Trinta e oito cepas de S. Enteritidis foram isoladas de pacientes atendidos no Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, entre os anos de 1996 e 1998. As cepas foram isoladas de fezes (31 amostras), sangue (quatro amostras) e outros fluidos (três amostras). As cepas de Salmonella foram isoladas utilizando-se métodos bacteriológicos de rotina, sorotipadas e ribotipadas. RESULTADOS: As 38 cepas de S. Enteritidis apresentaram na ribotipagem a separação das cepas em dois ribotipos: A (94,7% das amostras) e B (5,3% das amostras). DISCUSSÃO E CONCLUSÃO: Esses dados sugerem que grande parte dos pacientes (94,7%) foi infectada pela mesma cepa. Essa cepa pode ser endêmica na comunidade de Ribeirão Preto ou os pacientes foram expostos a uma fonte comum de infecção.

BACKGROUND: The approach generally employed in leading laboratories worldwide to identify strains of Salmonella is to detect epidemiological markers by serotyping and molecular techniques. These molecular methods are important in sanitary surveillance and lead to the source of infection. OBJECTIVES: The aim of the present study is to characterize Salmonella Enteritidis strains by ribotyping. MATERIAL AND METHODS: Thirty-eight strains of S. Enteritidis were isolated from in patients at the university hospital of Universidade de São Paulo, Ribeirão Preto, SP, Brazil, between 1996 and 1998. These strains were isolated from stools (31 samples), blood (4 samples) and other body fluids (3 samples), using routine bacteriological methods, and were serotyped and ribotyped. RESULTS: The 38 strains of serotype S. Enteritidis were shown by the ribotyping to belong to two ribotypes: A (94.7% of the samples) and B (5.3%). DISCUSSION AND CONCLUSION: These results suggest that the majority of patients (94.7%) were infected by the same strain. This strain could be endemic in the Ribeirão Preto community, or these patients may have been exposed to a common source of infection.

Com os avanços terapêuticos que incluem o mesilato de imatinibe, o transplante de medula óssea e a infusão de linfócito do doador, a perspectiva de vida dos portadores de leucemia mielóide crônica (LMC) tem aumentado significativamente e a doença pode não ser fatal. No entanto, os mecanismos biológicos que privilegiam a seleção das células hematopoéticas malignas sobre as células normais na LMC, responsáveis pelo insucesso terapêutico em muitos casos, ainda não estão totalmente esclarecidos. Alterações no processo de apoptose celular e escape das células leucêmicas à resposta imune antitumoral poderiam explicar, em parte, a vantagem seletiva dessas células. O processo de apoptose celular pode ser desencadeado pelas vias intrínseca ou extrínseca. A extrínseca é dependente da interação de receptores de morte celular, como a ligação do receptor Fas com seu receptor, o Fas ligante (FasL). A expressão diminuída de Fas e aumentada de FasL na célula leucêmica podem aumentar sua sobrevida tornando-a resistente à apoptose. Esse artigo descreve a relação entre LMC e o sistema Fas/FasL, sua possível importância no prognóstico e escape das células leucêmicas à resposta imune.

With therapeutic advances that include imatinib mesylate, bone marrow transplantation and donor lymphocyte infusion, life expectancy of chronic myeloid leukemia carriers has increased significantly and the disease might not be fatal. However, the biological mechanisms that favor the selection of malignant clone cells over normal cells, in most cases responsible for the lack of therapeutic success, are still unclear. Alterations in cellular apoptosis process and escape of the leukemic cells from the anti-tumor immune response can explain, in part, the selective advantages of these cells. The apoptosis process or programmed cell death can be triggered by intrinsic or extrinsic pathways. The extrinsic is dependent on the interaction of cell death receptors, such as the Fas receptor and its agonist, the Fas ligand (FasL). A diminished expression of Fas and increased of FasL in leukemic cell may increase its survival, thereby making it resistant to apoptosis. This paper describes the relation between chronic myeloid leukemia and the Fas/FasL system and its possible importance in prognosis and in escape of the leukemic cells from the immune system.