Assuntos
Leucemia Mielomonocítica Aguda/microbiologia , Micoses/complicações , Antifúngicos/uso terapêutico , Candida glabrata/efeitos dos fármacos , Candida glabrata/isolamento & purificação , Farmacorresistência Fúngica , Equinocandinas/uso terapêutico , Evolução Fatal , Humanos , Leucemia Mielomonocítica Aguda/complicações , Leucemia Mielomonocítica Aguda/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/patologia , Rhizomucor/efeitos dos fármacos , Rhizomucor/isolamento & purificação , Baço/irrigação sanguínea , Baço/microbiologia , Baço/patologiaRESUMO
Undifferentiated U937 cells are non-permissive for herpes simplex virus (HSV) infection but can be rendered permissive by treatment with phorbol myristate acetate (PMA), which causes them to differentiate to a macrophage-like phenotype. Following infection with HSV, both PMA--treated and untreated cells correctly transcribe the viral immediate-early genes at levels comparable to those observed in fully permissive cell types, but immediate-early RNA and protein are detected only in the PMA-treated cells. Hence PMA acts by relieving an early block to HSV infection caused by the rapid turnover of immediate-early RNA. This block is not caused by the production of soluble inhibitors and can also be relieved by treatment with other agents that cause macrophage differentiation such as 1, 25 dihydroxycholecalciferol. These findings therefore indicate that the non-permissivity of undifferentiated U937 cells for HSV is mediated by post-transcriptional regulation of immediate-early gene expression.
Assuntos
Herpes Simples/fisiopatologia , Fagócitos/fisiologia , Linhagem Celular , Transformação Celular Neoplásica/efeitos dos fármacos , Transformação Celular Neoplásica/patologia , Di-Hidroxicolecalciferóis/farmacologia , Regulação Viral da Expressão Gênica/fisiologia , Genes Reguladores/fisiologia , Genes Virais/fisiologia , Herpes Simples/metabolismo , Humanos , Leucemia Mielomonocítica Aguda/metabolismo , Leucemia Mielomonocítica Aguda/microbiologia , Leucemia Mielomonocítica Aguda/patologia , Fagócitos/metabolismo , RNA Viral , Simplexvirus/genética , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/fisiologiaRESUMO
Numerous investigators have demonstrated that derangements in serum transferrin and iron can contribute to susceptibility to infection, but the complexity and imprecision of assays have impeded both research and development of clinical testing in this area. This article describes an automated assay for measuring the microbial inhibitory activity of transferrin in serum and its use in patients with acute myelogenous leukemia (AML) and in normal controls. The assay measured the ability of heat-inactivated serum to inhibit the growth of an antibiotic-resistant strain of Pseudomonas aeruginosa. The serum dilutions were prepared in a special low iron chemically defined broth. An inhibition index, the reciprocal of the serum dilution producing 50% inhibition of bacterial growth when compared with the growth in broth alone, was determined. The results showed the serum from the patients with leukemia had a significantly lower inhibition index than that of controls (16 +/- 11 vs. 35 +/- 13, P less than 0.01). In addition, they had higher serum iron levels (162 +/- 65 vs. 75 +/- 27, P less than 0.01), lower serum transferrin levels (231 +/- 65 vs. 309 +/- 71, P less than 0.01), and higher percentage saturation of transferrin with iron (59 +/- 21 vs. 20 +/- 8, P less than 0.01) than did controls. Because the assay uses equipment available in many clinical laboratories, it could be developed for routine use as an index of susceptibility to infection in selected patients.
Assuntos
Atividade Bactericida do Sangue , Ferro/sangue , Leucemia Mielomonocítica Aguda/sangue , Testes de Sensibilidade Microbiana/métodos , Transferrina/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Técnicas In Vitro , Leucemia Mielomonocítica Aguda/microbiologia , Masculino , Pseudomonas aeruginosa/crescimento & desenvolvimentoRESUMO
Chromosomal translocation often results in aberrant activation of the genes with oncogenic potential and, thus, plays an important role in leukemogenesis. We report a unique case of acute myelomonocytic leukemia carrying a rare reciprocal translocation, t(3;12)(q26;p13). This patient displayed typical clinical features of 3q21q26 syndrome such as abnormal thrombopoiesis and rapid disease progression. Blastic cells from the patient strongly expressed the EVI1 gene, which is located on 3q26 and is normally suppressed in bone marrow cells. Expression of the TEL gene, located on 12p13, was also observed, but fusion transcript between two genes was not found. No structural alterations of the EVI1 and TEL genes were detected by Southern blot and PCR analyses. We reviewed previous literature and found 10 other cases with t(3;12)(q26;p13). These patients comprise a unique disease group with features including dyshematopoiesis and poor prognosis. However, characteristics related to 3q21q26 syndrome were observed only in the present case. Further investigation is required to elucidate the molecular basis of this particular entity.
Assuntos
Cromossomos Humanos Par 12/ultraestrutura , Cromossomos Humanos Par 3/ultraestrutura , Leucemia Mielomonocítica Aguda/genética , Proto-Oncogenes , Proteínas Repressoras , Translocação Genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 3/genética , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Coagulação Intravascular Disseminada , Elementos Facilitadores Genéticos , Evolução Fatal , Regulação Leucêmica da Expressão Gênica , Humanos , Cariotipagem , Leucemia Mielomonocítica Aguda/microbiologia , Leucemia Mielomonocítica Aguda/patologia , Proteína do Locus do Complexo MDS1 e EVI1 , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Contagem de Plaquetas , Prognóstico , Proteínas Proto-Oncogênicas c-ets , RNA Mensageiro/biossíntese , RNA Neoplásico/biossíntese , Síndrome , Trombocitose/etiologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Variante 6 da Proteína do Fator de Translocação ETSRESUMO
Plasma samples of patients with AML or AMMoL were tested for antibodies reacting with gp70 antigens of BaEV and GaLV as well as for antibodies neutralizing BaEV or GaLV. Both frequency and titer values of antibodies were higher in remission than in blastosis. Neutralizing activity could be detected only in those plasma samples which contained antibodies to the appropriate gp70 antigen. The data suggest the presence of retroviruses in humans as antigenic stimuli for the immune system in AML and AMMoL.
Assuntos
Anticorpos Antivirais/análise , Leucemia Mieloide Aguda/microbiologia , Leucemia Mielomonocítica Aguda/microbiologia , Retroviridae/imunologia , Linhagem Celular , Humanos , Leucemia Mieloide Aguda/imunologia , Leucemia Mielomonocítica Aguda/imunologia , Testes de NeutralizaçãoRESUMO
An association of HTLV-I virus with myelomonocytic leukemia was established by serologic and molecular-biologic procedures. Antibodies to one or two HTLV-I proteins were identified in 10 out of 30 patients with myelomonocytic leukemia; both antibodies to certain HTLV-I proteins and an integrated provirus were detected in 3 cases. Upon examination of donor blood, antibodies to one or two HTLV-I proteins were found in 0.8% cases, but only 0.3% of the examined donors were found positive to HTLV-I. This finding points to the presence of said virus in the population of Latvia.
Assuntos
Infecções por HTLV-I/complicações , Leucemia Mieloide/microbiologia , Idoso , Feminino , Anticorpos Anti-HTLV-I/análise , Infecções por HTLV-I/imunologia , Humanos , Cariotipagem , Leucemia Mieloide/imunologia , Leucemia Mielomonocítica Aguda/microbiologia , Leucemia Mielomonocítica Crônica/microbiologia , Masculino , Pessoa de Meia-IdadeAssuntos
Leucemia Mielomonocítica Aguda/microbiologia , Neutrófilos/microbiologia , Infecções Estafilocócicas/etiologia , Staphylococcus/isolamento & purificação , Adulto , Coagulase , Evolução Fatal , Humanos , Leucemia Mielomonocítica Aguda/complicações , Masculino , Resistência a Meticilina , RecidivaRESUMO
We retrospectively analyzed the antifungal usage in children with acute myeloid leukemia (AML). Overall, 211 of 304 patients (69.4%) received a total of 389 antifungal treatment episodes. In 234 episodes, initial antifungal treatment consisted of amphotericin B [as monotherapy, n = 193; median dosage (range) of amphotericin B deoxycholate 0.6 mg/kg per day (0.02-1.5 mg/kg per day) and of liposomal amphotericin B 3.0 mg/kg per day (0.6-30 mg/kg per day)], in 149 episodes of fluconazole [as monotherapy, n = 143; 5 mg/kg per day (1-29 mg/kg per day)], in 40 of flucytosine [as monotherapy, n = 1; 150 mg/kg per day (40-370 mg/kg per day)], and in 9 of itraconazole [as monotherapy, n = 8; 6 mg/kg per day (1.6-20 mg/kg per day)]. We conclude that the majority of children with AML receives at least one episode of antifungal therapy. Inappropriate dosing and combination of antimycotics need to be addressed in future educational measures.
Assuntos
Antifúngicos/administração & dosagem , Aspergilose/complicações , Aspergilose/tratamento farmacológico , Candidíase/complicações , Candidíase/tratamento farmacológico , Leucemia Mielomonocítica Aguda/microbiologia , Adolescente , Anfotericina B/administração & dosagem , Criança , Feminino , Fluconazol/administração & dosagem , Flucitosina/administração & dosagem , Humanos , Lactente , Recém-Nascido , Itraconazol/administração & dosagem , Masculino , Estudos RetrospectivosRESUMO
Hortaea werneckii is an environmental dematiaceous fungus found in the halophilic environment. It causes tinea nigra. We report the isolation of H. werneckii from blood and splenic abscess of two patients with acute myelomonocytic leukaemia. H. werneckii grew at room temperature but not at 37 degrees C, it was identified by biochemical tests, growth characteristics and the presence of conspicuous collarette intercalary on dividing yeast cells. The use of specific oligonucleotide primer Hor-F (5'-TGGACACCTTCA TAACTCTTG-3') and Hor-R (5'-TCACAACGCTTAGAGACGG-3') confirmed the two isolates were H. werneckii. The sequence for 281 nucleotide of HW299 and HW403 were 99% identical but differed only in one nucleotide. In vitro anti-fungal susceptibility testing showed that the isolates were resistant to amphotericin B and flucytosine.
Assuntos
Fungemia/microbiologia , Leucemia Mielomonocítica Aguda/microbiologia , Fungos Mitospóricos/genética , Fungos Mitospóricos/isolamento & purificação , Esplenopatias/microbiologia , Sequência de Bases , DNA Fúngico/química , DNA Fúngico/genética , Feminino , Humanos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Fungos Mitospóricos/ultraestrutura , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Sepse , Alinhamento de SequênciaRESUMO
A 10-year-old girl diagnosed with acute myeloid leukemia FAB M4 failed to achieve remission following several courses of induction chemotherapy. From the first course of chemotherapy the patient had continuous marrow aplasia, managed by a total of 57 granulocyte transfusions. After reinduction and reduced-intensity conditioning including fludarabine, Campath-1H, and melphalan, the patient received unmanipulated marrow from an HLA-matched unrelated donor. Leukocyte and platelet engraftment was observed on day +18 and +50, respectively. Graft-versus-host disease did not occur. The patient is alive and well in complete remission 18 months after transplantation with complete donor chimerism.
Assuntos
Anemia Aplástica/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/prevenção & controle , Leucemia Mielomonocítica Aguda/terapia , Recidiva Local de Neoplasia/terapia , Condicionamento Pré-Transplante , Vidarabina/análogos & derivados , Alemtuzumab , Anemia Aplástica/terapia , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/administração & dosagem , Criança , Feminino , Granulócitos/patologia , Humanos , Leucemia Mielomonocítica Aguda/microbiologia , Melfalan/administração & dosagem , Recidiva Local de Neoplasia/microbiologia , Indução de Remissão , Quimeras de Transplante , Transplante Homólogo , Vidarabina/administração & dosagemRESUMO
The levels of intracisternal A-particle (IAP) mRNA were analyzed in a variety of myelomonocytic leukemia cell lines, peritoneally derived macrophages, and normal hemopoietic progenitors induced to differentiate. In both normal and leukemic cells, the highest level of IAP message was found in cells at an intermediate stage of myelomonocytic differentiation, namely, the promyelomonocyte. These results indicate that IAP sequence transcription is regulated differentially during myelomonocytic cell development and that in general, the expression pattern is preserved in leukemic cell lines in vitro. In addition, Northern (RNA) analysis detected only type I IAP transcripts as the major IAP message and the expressed IAP subtypes varied in certain cell lines. This is the first comprehensive study of IAP expression in the myelomonocytic lineage and provides a useful system to study the biology of IAPs.
Assuntos
Genes de Partícula A Intracisternal , Leucemia Mielomonocítica Aguda/genética , Animais , Sequência de Bases , Transformação Celular Neoplásica , Vírus da Leucemia Murina de Friend/genética , Expressão Gênica , Humanos , Leucemia Mielomonocítica Aguda/microbiologia , Macrófagos/microbiologia , Camundongos , Dados de Sequência Molecular , Provírus/genética , Ratos , Vírus 40 dos Símios/genética , Células-Tronco/microbiologia , TATA Box , Células Tumorais CultivadasRESUMO
Infection due to the human immunodeficiency virus (HIV) has been complicated by the development of acute nonlymphocytic leukemia in five patients whose cases have previously been reported; other manifestations, including preleukemia, myelofibrosis, and myeloid hyperplasia, have also been reported in patients infected with HIV. We report the sixth case of an HIV-infected patient who developed acute myelomonocytic leukemia; HIV infection was documented by tests for serum antibodies (enzyme-linked immunosorbent assay and western blotting), by a markedly elevated p24 antigen level in plasma, and by cultures of CSF and peripheral blood that were positive for HIV. Furthermore, myelomonoblasts that were cultured without the addition of growth factors displayed evidence of HIV replication through the presence of p24 antigen and reverse transcriptase activity, both of which lasted for 4 weeks in the supernatant fluid of the cell cultures. This case report provides the first data indicating that HIV may infect myelomonoblasts in vivo and represents the sixth reported case of an association between HIV infection and pure acute nonlymphocytic leukemia.
Assuntos
Infecções por HIV/complicações , HIV/isolamento & purificação , Leucemia Mielomonocítica Aguda/complicações , Adulto , Western Blotting , Líquido Cefalorraquidiano/microbiologia , Ensaio de Imunoadsorção Enzimática , Produtos do Gene gag/sangue , Anticorpos Anti-HIV/sangue , Antígenos HIV/sangue , Proteína do Núcleo p24 do HIV , Humanos , Leucemia Mielomonocítica Aguda/microbiologia , Masculino , Células Tumorais Cultivadas , Proteínas do Core Viral/sangueRESUMO
A 57-year-old man with acute myeloid leukemia (AML) French-American-British (FAB) 4 developed disseminated invasive cerebral and pulmonary aspergillosis during postinduction aplasia. According to international consensus, infection was categorized as probable (two host factors: deep neutropenia for >10 days and refractory fever for >96 h; major clinical criteria of lower respiratory tract and CNS invasive fungal infection; positive results for galactomannan antigen in three blood samples). After the failure of standard amphotericin-based therapy, the spectacular regression of multifocal brain and lung lesions was rapidly achieved under a caspofungin acetate/voriconazole combination. Further permanent caspofungin maintenance with voriconazole added during aplasia periods permitted two consolidation courses and autograft-based intensification without any delay.