Assuntos
Elementos Facilitadores Genéticos , Hemoglobina H/genética , alfa-Globinas/genética , Talassemia alfa/genética , Adulto , Alelos , Cromatina/genética , Cromatina/ultraestrutura , Cromossomos Humanos Par 16/genética , Cromossomos Humanos Par 16/ultraestrutura , Eritroblastos/patologia , Eritropoese , Feminino , Deleção de Genes , Regulação da Expressão Gênica , Genótipo , Hemoglobina E/genética , Hemoglobina H/análise , Humanos , Masculino , Linhagem , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Deleção de Sequência , Suriname/etnologia , alfa-Globinas/biossíntese , Talassemia alfa/sangue , Globinas beta/genéticaRESUMO
BACKGROUND: The Wilms Tumor gene (WT1) encodes a transcription factor involved in kidney development and malignancy. WT1 expression in a subpopulation of early CD34+ cells has suggested its involvement in hematopoiesis. WT1 is aberrantly expressed in leukemias. High expression of WT1 at diagnosis has been associated with unfavorable prognosis in adult acute myeloid leukemia (AML). The prognostic relevance of WT1 expression in pediatric AML was evaluated in only one study, including 47 patients, which showed that very low levels of WT1 at presentation were associated with an excellent outcome. To test the validity of these findings we measured levels of WT1 in 41 newly diagnosed pediatric AML of the non-M3 FAB subtype. PROCEDURE: Patients were treated according to an AML-BFM 83-based protocol in a single institution. Mononucleated cells obtained from presentation BM aspirates were cryopreserved and later thawed and used for total RNA extraction and cDNA synthesis. The quantitative assessment of WT1 transcripts was made by real-time PCR (RQ-PCR). WT1 transcripts values were normalized with respect to the number of ABL transcripts. RESULTS: WT1 levels were significantly higher in patients bearing favorable chromosome abnormalities, t(8;21) and inv(16) (P = 0.002). Higher levels of WT1 expression were unexpectedly associated with a higher probability of overall survival by Cox regression analysis (P = 0.002). Multivariate regression analysis could not discriminate between the effects of WT1 and cytogenetics on survival. CONCLUSIONS: Higher WT1 expression was associated with favorable cytogenetics subtypes and accordingly with better outcome in children with AML in this study.
Assuntos
Genes do Tumor de Wilms , Leucemia Mieloide/genética , Doença Aguda , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Brasil/epidemiologia , Criança , Pré-Escolar , Inversão Cromossômica , Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 21/ultraestrutura , Cromossomos Humanos Par 8/ultraestrutura , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Feminino , Seguimentos , Regulação Leucêmica da Expressão Gênica , Humanos , Lactente , Leucemia Mieloide/tratamento farmacológico , Leucemia Mieloide/mortalidade , Leucemia Promielocítica Aguda/genética , Leucemia Promielocítica Aguda/mortalidade , Masculino , Proteínas de Neoplasias/biossíntese , Prognóstico , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sobrevida , Translocação Genética , Proteínas WT1/biossínteseRESUMO
Roberts syndrome (RS) is associated with a characteristic constitutive heterochromatin anomaly, namely, at metaphase the centromeres and heterochromatic segments appear split. In addition to this cytogenetic phenomenon, known as the RS effect, several other cytological features, especially affecting mitotic chromosome disjunction, are also observed. Applying FISH to interphase nuclei, we investigated the replication patterns of homologous alphoid centromeric DNA of chromosomes 9, 11, 16 and 17 in three patients showing the RS effect and in four normal individuals. A tendency for homologous centromeres to replicate asynchronously was observed in RS patients. This tendency was more evident in chromosomes 9 and 16, with large heterochromatic blocks and particularly subject to RS effect. This asynchrony could reflect a more generalized alteration in repetitive DNA replication timing that, in turn, would prevent the establishment of proper cohesion between sister chromatid heterochromatin, leading to the RS effect.
Assuntos
Anormalidades Múltiplas/genética , Centrômero/metabolismo , Cromossomos Humanos/metabolismo , Replicação do DNA , DNA Satélite/biossíntese , Anormalidades Múltiplas/metabolismo , Cromossomos Humanos/ultraestrutura , Cromossomos Humanos Par 11/metabolismo , Cromossomos Humanos Par 11/ultraestrutura , Cromossomos Humanos Par 16/metabolismo , Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 17/metabolismo , Cromossomos Humanos Par 17/ultraestrutura , Cromossomos Humanos Par 9/metabolismo , Cromossomos Humanos Par 9/ultraestrutura , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/metabolismo , Feminino , Genes Recessivos , Heterocromatina/metabolismo , Humanos , Hibridização in Situ Fluorescente , Deformidades Congênitas dos Membros/genética , Deformidades Congênitas dos Membros/metabolismo , Masculino , Metáfase , SíndromeRESUMO
A 2 years and 9 months old female patient, with the diagnosis of Weaver syndrome is reported. The proband presents persistent pre and post-natal overgrowth, asynchronic advanced bone age, particular facies, (macrocephaly, ocular hypertelorism, micrognathia, large ears), bilateral widening of the distal femoral metaphysis, bilateral tibia vara, prominent fetal fingerpads, clinodactyly, development delay, low pitched and hoarse cry, nonspecific cortical atrophy, dilation of the ventricles and vermix hypoplasia. The differential diagnosis with other overgrowth syndromes is discussed. The possibility of uniparental disomy and genetic imprinting as the basic genetic defect in the Weaver syndrome is suggested. The patient reported here appears to be the first case in the Venezuelan literature.
Assuntos
Anormalidades Múltiplas , Transtornos do Crescimento , Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/epidemiologia , Anormalidades Múltiplas/genética , Determinação da Idade pelo Esqueleto , Pré-Escolar , Cromossomos Humanos Par 16/ultraestrutura , Disostose Craniofacial/diagnóstico , Disostose Craniofacial/epidemiologia , Disostose Craniofacial/genética , Diagnóstico Diferencial , Feminino , Impressão Genômica , Transtornos do Crescimento/diagnóstico , Transtornos do Crescimento/epidemiologia , Transtornos do Crescimento/genética , Deformidades Congênitas da Mão/diagnóstico , Deformidades Congênitas da Mão/epidemiologia , Deformidades Congênitas da Mão/genética , Humanos , Cariotipagem , Síndrome , Venezuela/epidemiologiaRESUMO
Se estudió la frecuencia de los polimorfismos de la heterocromatina constitutiva con bandas C de los cromosomas 1, 9 y 16 en dos poblaciones de mestizos mexicanos. Para la clasificación del tamaño de la heterocromatina se utilizó un método semicuantitativo que mostró se reproducible, simple y útil para ser usado rutinariamente. Se comparan nuestros hallazgos con los observados en otras poblaciones.
Assuntos
Humanos , Masculino , Cromossomos Humanos Par 16/ultraestrutura , Cromossomos Humanos Par 1/ultraestrutura , Cromossomos Humanos Par 9/ultraestrutura , Heterocromatina/ultraestrutura , Polimorfismo Genético/genética , Grupos Raciais/genética , México/etnologiaRESUMO
The frequency of heterochromatic polymorphisms on C-banded chromosomes 1, 9 and 16 in two inter-racial Mexican populations was analyzed. Secondary constriction (qh) regions were classified according to a semi-quantitative procedure which showed to be simple and convenient. We compare our results with those in other populations.