RESUMO
Sensitivities to drugs acting on cells in culture can be measured as dose-response curves, provided a quantitative assay is available for a relevant cell function. We have used two such assays in the study of the blast cells of acute myeloblastic leukemia. Colony formation in culture with methylcellulose detects principally terminal divisions, while growth of clonogenic cells in suspension reflects self-renewal. In a previous study different cytosine arabinoside and 5-azacytidine dose-response curves were obtained with the two assays. For the former the slope of the dose-response curve measured in suspension was steeper than that obtained using the clonogenic assay. For the latter, 5-azacytidine, the relationship between sensitivity in suspension and in methylcellulose was reversed. Further, for cytosine arabinoside, sensitivity in suspension but not in methylcellulose was associated with successful remission-induction. In this article we report an association between 5-azacytidine sensitivity in suspension and successful remission induction, for patients treated only with high-dose cytosine arabinoside. There was no correlation between the 5-azacytidine dose-response curve in methyl-cellulose and clinical outcome. A model is presented that may explain these findings, based on the hypothesis that there are genetic mechanisms responsible for blast cell renewal.
Assuntos
Azacitidina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular/efeitos dos fármacos , Ensaio de Unidades Formadoras de Colônias , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Metilcelulose , Pessoa de Meia-IdadeRESUMO
A patient with myelodysplastic syndrome (refractory anemia) with marked and persistent reticulocytosis is presented. A referring diagnosis of hemolytic disease had been made. However, the 51Cr red cell survival was normal (T1/2 24 days). Reticulocyte morphology, red cell creatine content, and in vitro reticulocyte survival studies have suggested that the reticulocytosis arose as a consequence of delayed maturation of the reticulocytes. Two patients with myelodysplastic syndrome and delayed reticulocyte maturation have previously been described; in both patients, however, red cell survival was also shortened. Anemia with reticulocytosis, mimicking hemolytic disease, may be an unusual presentation of myelodysplastic syndrome.
Assuntos
Anemia Hemolítica/diagnóstico , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Reticulócitos/patologia , Idoso , Anemia Hemolítica/sangue , Anemia Hemolítica/patologia , Diferenciação Celular/fisiologia , Sobrevivência Celular/fisiologia , Radioisótopos de Cromo , Creatinina/análise , Diagnóstico Diferencial , Feminino , Humanos , Síndromes Mielodisplásicas/patologia , Reticulócitos/químicaRESUMO
An adult with long-standing neutropenia had the functional granulocyte abnormalities typical of the lazy leucocyte syndrome. Scanning electron microscopy of the patient's neutrophils showed alteration in the surface configuration of the cell with coarsening of the normal fine ruffles and the appearance of knob-like projections. Similar functional and anatomical changes were induced in normal neutrophils by treatment with vinblastine. The lazy leucocyte syndrome may be a consequence of altered membrane microfilamentous protein structure or function, and undue rigidity of the affected neutrophils may explain the clinicopathological features of the disease.
Assuntos
Agranulocitose/patologia , Neutropenia/patologia , Neutrófilos/ultraestrutura , Adulto , Membrana Celular/efeitos dos fármacos , Membrana Celular/ultraestrutura , Quimiotaxia de Leucócito , Feminino , Humanos , Microscopia Eletrônica de Varredura , Neutropenia/fisiopatologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/fisiologia , Síndrome , Vimblastina/farmacologiaRESUMO
A case of idiopathic acquired sideroblastic anaemia transforming to acute myelofibrosis is reported. The appearance of atypical megakaryocytic proliferation in idiopathic acquired sideroblastic anaemia may presage the development of an acute myelofibrotic phase of this usually chronic disease.
Assuntos
Anemia Sideroblástica/complicações , Mielofibrose Primária/etiologia , Doença Aguda , Idoso , Anemia Sideroblástica/patologia , Divisão Celular , Humanos , Masculino , Megacariócitos/patologia , Mielofibrose Primária/patologiaRESUMO
A second example of chronic myeloid leukemia showing translocation of material from the long arm of chromosome #22 to the long arm of chromosome #21, ( 21q +:22q-), is reported. The patient presented with the typical clinico-pathologic features of the disease.
Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos , Cromossomos Humanos 21-22 e Y , Leucemia Mieloide/genética , Adulto , Medula Óssea/fisiopatologia , Células Cultivadas , Bandeamento Cromossômico , Feminino , Humanos , Cariotipagem , Linfócitos/fisiologiaRESUMO
A patient with chronic myeloid leukemia is described in whom a novel complex translocation was found among chromosomes #4, #9, and #22, resulting in a "masked" Philadelphia chromosome. The breakpoint in chromosome #4 (band q21) is in the same region as the breakpoint seen in the t(4;11), which is associated with some forms of acute leukemia.
Assuntos
Cromossomos Humanos 21-22 e Y , Cromossomos Humanos 4-5 , Cromossomos Humanos 6-12 e X , Leucemia Mieloide/genética , Cromossomo Filadélfia , Translocação Genética , Adulto , Feminino , HumanosRESUMO
We report a case of acute monocytic leukemia (FAB-5a) with a very aggressive clinical course and multiple chromosomal abnormalities. There were several sublines, each with trisomy 8 and a translocation involving 3q13.3 as a common breakpoint region. This region is an uncommon site of chromosomal breakage in malignancies and has not hitherto been reported as a breakpoint site in "jumping" translocations.
Assuntos
Cromossomos Humanos Par 3 , Leucemia Monocítica Aguda/genética , Translocação Genética , Idoso , Antígenos CD/análise , Cromossomos Humanos Par 8 , Humanos , Cariotipagem , Leucemia Monocítica Aguda/imunologia , Masculino , TrissomiaRESUMO
A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 5 , Trombocitemia Essencial/genética , Biópsia , Medula Óssea/ultraestrutura , Feminino , Humanos , Pessoa de Meia-Idade , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/patologiaAssuntos
Transplante de Medula Óssea , Reação Enxerto-Hospedeiro , Adulto , Agamaglobulinemia/cirurgia , Feminino , Doença Enxerto-Hospedeiro , Humanos , Lactente , Leucemia Linfoide/cirurgia , Leucemia Mieloide Aguda/cirurgia , Masculino , Ontário , Imunologia de Transplantes , Transplante HomólogoRESUMO
End-stage renal disease is treated by long-term dialysis when renal transplantation is not feasible. At a late stage in the disease, for a variety of reasons, dialysis is frequently stopped. This is one of the most common causes of death in dialysis patients. Ethical issues related to withdrawal of dialysis are therefore commonly encountered in nephrology practices. A case study involving discussions to forego dialysis in an incompetent patient is presented, and the ethical issues raised by this case, particularly related to the concepts of medical futility, informed choice, and justice are discussed. Finally, procedural approaches are suggested that will help to address the ethical problems raised and to assist in decision making at the time that the discontinuation of dialysis is being considered.
Assuntos
Ética Médica , Falência Renal Crônica/terapia , Futilidade Médica , Diálise Peritoneal , Idoso , Eutanásia Passiva , Feminino , Humanos , Consentimento Livre e Esclarecido , Competência Mental , Ordens quanto à Conduta (Ética Médica)RESUMO
Blast crisis, closely resembling acute leukemia, is the usual terminal event in chronic myeloid leukemia. Using physical ("fingerprint") and cultural (colony-forming) methods, we have demonstrated distinctive patterns in the stable phase of chronic myeloid leukemia and in blast crisis. An unusual fingerprint alteration preceding the onset of the terminal phase is noted, and cell culture perturbation is evident at different stages of the disease. Our findings indicate that the application of these methods to the study of hemopoietic disorders is valid, and suggest that the use of such techniques may allow a better understanding of the complex cellular events occurring in the course of chronic myeloid leukemia.
Assuntos
Doença Aguda , Células da Medula Óssea , Medula Óssea/patologia , Leucemia Mieloide/patologia , Adulto , Idoso , Separação Celular , Células Cultivadas , Computadores , Feminino , Granulócitos/patologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Levamisole, which has immunostimulant activity, is now being used to treat some forms of cancer. We report that the drug enhances granulocyte colony formation. The mechanism of action appears to be partly through modulation of molecules on cell membranes. The molecular content of colony-stimulating activity (CSA) released into leucocyte-conditioned medium by cells of leukaemic and some preleukaemic patients can be quantitatively altered by levamisole, both in vitro and in vivo, but the CSA produced is qualitatively similar to that released by normal cells. The demonstrated levamisole enhancement of colony formation, and altered CSA types detected in leucocyte-conditioned medium, makes this drug a promising candidate for treatment of selected leukaemic states and in preleukaemia.
Assuntos
Células-Tronco Hematopoéticas/efeitos dos fármacos , Levamisol/farmacologia , Adulto , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Células Cultivadas , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura , Granulócitos/efeitos dos fármacos , Granulócitos/patologia , Humanos , Leucemia/patologia , Masculino , Pré-Leucemia/patologiaRESUMO
Human bone marrow obtained from patients with neutropenia contains a cell population which is absent or diminished in normal marrow. The abnormal population is composed of cells of volume 200-300 mum3 which sediment at 5-5 to 8-5 mm/h. Normal marrow contains one cell class giving rise to increased numbers of grnaulocyte colonies after mass culture, while marrow obtained from neutropenic patients, or from patients with marrow regeneration, shows two such populations; one of these cell classes corresponds to the abnormally large cells demonstrated on velocity sedimentation analysis. This population of large cells may represent a group of either self-renewing cells related to the committed granulocyte progenitors or the pluripotent stem cell.
Assuntos
Agranulocitose/patologia , Células-Tronco Hematopoéticas/patologia , Neutropenia/patologia , Adulto , Medula Óssea/patologia , Células da Medula Óssea , Contagem de Células , Células Clonais , Granulócitos , Humanos , Neutropenia/sangueRESUMO
The colony-stimulating activity detected by its ability to promote colony formation by human granulopoietic progenitor cells was partially purified from medium conditioned by human peripheral leucocytes. The purification procedure utilized (NH4)2SO4 precipitation, DEAE-cellulose chromatography, hydroxyapatite chromatography and gel filtration on Sephadex G-150 and yielded a purification of about 1000-fold. The medium from cultures of non-leukaemic cells contained three molecular species of colony-stimulating activity with approximate molecular weights of 93000, 36500 and 14700. On the basis of their sensitivity to enzymes, these species of activity appeared to be proteins. In contrast, medium from cultures of leukaemic cells contained only one detectable molecular species with colony-stimulating activity, usually with an approximate molecular weight of 36500. The results are discussed in relation to concurrent studies on the association of the different species of colony-stimulating activity with the cell surface membrane.
Assuntos
Divisão Celular , Glicoproteínas/isolamento & purificação , Granulócitos , Leucócitos/análise , Células da Medula Óssea , Membrana Celular/metabolismo , Cromatografia DEAE-Celulose , Humanos , Leucemia/sangue , Peso MolecularRESUMO
Cell culture methods applied to the study of acute leukemia have indicated the presence of many abnormalities. Utilizing this knowledge, we have applied cell culture techniques to the evaluation of a patient population with a recognized risk of developing leukemia. We demonstrate that cultural abnormalities present in some patients with sideroblastic anemia are similar to those seen in acute leukemia, and that these perturbations may be shown before leukemia develops. This study suggests that cell culture abnormalities may reflect mechanisms operative in vivo, and preceding the development of overt leukemia.