RESUMEN
Acute lymphoblastic leukemia (ALL) accounts for approximately 80% of all acute leukemias during childhood. Chromosomal anomalies resulting from gene fusion, which are frequent in leukemias, create hybrid transcripts, the great majority of which encode transcription factors. We analyzed 88 pediatric patients (median age 7.3 years) who had B-lineage acute lymphoblastic leukemia (B-ALL), using reverse transcriptase-polymerase chain reaction, to look for gene fusion transcripts of TEL/AML1, E2A/PBX1, BCR/ABL p190, and MLL/AF4. The frequencies of these transcripts were 21.21, 9.68, 3.03, and 0%, respectively. All positive cases had a common B-ALL immunophenotype. The low frequency of the TEL/AML1 transcript that is found in developing countries, such as Brazil, may be due to the low incidence of leukemia; this would support Greaves' hypothesis.
Asunto(s)
Aberraciones Cromosómicas , Mutación , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Brasil , Linaje de la Célula , Niño , Bases de Datos Genéticas , Femenino , Humanos , Inmunofenotipificación , Masculino , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismoRESUMEN
Infant acute leukemia (IAL) frequently involves breakage and recombination of the MLL gene with one of several potential partner genes. These gene fusions arise in utero and are similar to those found in leukemias secondary to chemotherapy with inhibitors of topoisomerase II (topo-II). This has led to the hypothesis that in utero exposures to chemicals may cause IAL via an effect on topo-II. We report a pilot case-control study of IAL across different countries and ethnic groups. Cases (n = 136) were population-based in most centers. Controls (n = 266) were selected from inpatients and outpatients at hospitals serving the same populations. MLL rearrangement status was derived by Southern blot analysis, and maternal exposure data were obtained by interviews using a structured questionnaire. Apart from the use of cigarettes and alcohol, very few mothers reported exposure to known topo-II inhibitors. Significant case-control differences were apparent for ingestion of several groups of drugs, including herbal medicines and drugs classified as "DNA-damaging," and for exposure to pesticides with the last two being largely attributable, respectively, to one nonsteroidal anti-inflammatory drug, dipyrone, and mosquitocidals (including Baygon). Elevated odds ratios were observed for MLL+ve (but not MLL-ve) leukemias (2.31 for DNA-damaging drugs, P = 0.03; 5.84 for dipyrone, P = 0.001; and 9.68 for mosquitocidals, P = 0.003). Although it is unclear at present whether these particular exposures operate via an effect on topo-II, the data suggest that specific chemical exposures of the fetus during pregnancy may cause MLL gene fusions. Given the widespread use of dipyrone, Baygon, and other carbamate-based insecticides in certain settings, confirmation of these apparent associations is urgently required.
Asunto(s)
Proteínas de Unión al ADN/genética , Inhibidores Enzimáticos/efectos adversos , Leucemia Mieloide/inducido químicamente , Leucemia-Linfoma Linfoblástico de Células Precursoras/inducido químicamente , Efectos Tardíos de la Exposición Prenatal , Proto-Oncogenes , Inhibidores de Topoisomerasa II , Factores de Transcripción , Enfermedad Aguda , Fusión Artificial Génica , Estudios de Casos y Controles , Inhibidores Enzimáticos/farmacocinética , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Recién Nacido , Leucemia Mieloide/genética , Masculino , Intercambio Materno-Fetal , Proteína de la Leucemia Mieloide-Linfoide , Proyectos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Embarazo , Factores de RiesgoRESUMEN
We analysed 67 samples from Brazilian children of diverse ethnic origins with acute lymphoblastic leukaemia (ALL) for the presence of the TEL-AML1 fusion gene transcripts using reverse transcription polymerase chain reaction (RT-PCR). All 12 positive cases (20% of the 60 B-cell precursor ALL) had common (CD10+) ALL with a mean age of 4 years (range 1-10 years). We conclude that the frequency, age, distribution and clinical features of the TEL-AML1 fusion gene-positive ALL is similar in the diverse ethnic backgrounds of the Brazilian children to that in other countries with predominantly white Caucasian or oriental ethnicity. Apparent exceptions to this generality are discussed.
Asunto(s)
Linfoma de Burkitt/genética , Frecuencia de los Genes , Leucemia-Linfoma de Células T del Adulto/genética , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Población Negra , Brasil , Linfoma de Burkitt/etnología , Niño , Preescolar , Subunidad alfa 2 del Factor de Unión al Sitio Principal , Femenino , Humanos , Lactante , Leucemia-Linfoma de Células T del Adulto/etnología , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/etnología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Población BlancaRESUMEN
OBJECTIVE: There are no studies on the prevalence of celiac disease (CD) in either Brazil or, as far as we know, South America. The aim of this study was to determine the prevalence of CD in healthy blood donors in the city of Brasilia, Brazil. METHODS: Sera were obtained, independently of age and gender, from an unselected group of 2045 blood donors attending the Hematological Center of Brasilia. An IgG antigliadin antibody (AGA) test was used as a first-level screening step, followed by IgA-AGA test, serum IgA antiendomysium (EMA), and total serum IgA determination performed in all sera showing abnormally high IgG-AGA results. Jejunal biopsy was suggested for all subjects showing at least one of the following: IgA-EMA positivity; IgG-AGA and IgA-AGA positivity; IgG-AGA positivity and selective IgA deficiency. AGA was determined by an enzyme-linked immunosorbent assay (ELISA) technique and IgA-EMA was ascertained by indirect immunofluorescence on cryostat sections of monkey esophagus. Jejunal mucosa samples were obtained with a Watson capsule. RESULTS: Sixty-two (3.03%) blood donors had IgG-AGA above the cut-off values. Fifty-eight individuals showed isolated high values of IgG-AGA, whereas four had simultaneously increased IgG and IgA-AGA. Three patients had positive IgA-EMA test (one with both IgG- and IgA-AGA and two with only IgG-AGA) and underwent jejunal biopsies that disclosed complete villous atrophy associated with an increased number of intraepithelial lymphocytes and hypertrophic criptae. In this study group, the prevalence of biopsy-proven celiac disease was 1.47 +/- 1.66 in 1000 subjects. CONCLUSIONS: We found a prevalence of undiagnosed CD of 1:681 among apparently healthy blood donors. These preliminary results support the view that CD is not a rare disease in Brazil.
Asunto(s)
Donantes de Sangre/estadística & datos numéricos , Enfermedad Celíaca/epidemiología , Comparación Transcultural , Adolescente , Adulto , Brasil/epidemiología , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , América del Sur/epidemiologíaRESUMEN
We report a new translocation t(8;22)(q22;q11) in a single case of epithelioid sarcoma. The band involved in chromosome 22 is the same found in 70-80% of the case of Ewing's sarcoma/peripheral neuroepithelioma (PNET) with cytogenetic characterization. The histologic characteristics of this tumor were typical for epithelioid sarcoma. Immunohistochemical stains were also entirely consistent with this diagnosis, including non-reactivity with P30/32MIC2, a specific marker for Ewing's sarcoma/primitive neuroepithelioma.
Asunto(s)
Cromosomas Humanos Par 22 , Cromosomas Humanos Par 8 , Antebrazo , Sarcoma/genética , Translocación Genética , Niño , Humanos , Masculino , Sarcoma/patologíaRESUMEN
Administration of the trypanocidal drug, Benznidazole (N-benzyl-2-nitro-imidazoleacetamide) to Trypanosoma cruzi-infected rabbits did not arrest the destructive Chagas' heart myocarditis. A typical feature of lymphocytic infiltrates associated with non-parasitized heart cell lysis was present in both treated and untreated groups of rabbits. Benznidazole-treated rabbits had their survival time shortened, probably as a consequence of Chagas' heart disease and of the development of lymphomas. The survival time of untreated T. cruzi-infected rabbits was 765 +/- 639 days and those treated with Benznidazole in the chronic phase of infection survived for 392 +/- 571 days. Malignant, non-Hodgkin's lymphomas were present in 38% of the rabbits that received the nitroarene therapy. Testicular atrophy was observed in 2 out of 10 nitroarene-treated rabbits. Benznidazole administration caused severe cell-mediated immunosuppression in T. cruzi-infected and BCG-immunized rabbits. Specific antibodies against the parasite and an unrelated antigen were detected in high levels, regardless of the nitroarene administration.