Citogenetica nas leucemias linfoides agudas /
Source: OAI


Orientador: Profª Drª Mara Albonei Dudeque Pianovski Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde, Programa de Pós-Graduação em Saúde da Criança e do Adolescente. Defesa: Curitiba, 2007 Inclui bibliografia

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    ABSTRACT: Identical infant twins with concordant leukemia were first described in 1882, and since that time many such pairs of infants and older children have been described. It has long been recognized that this situation offers a unique opportunity to identify aspects of the developmental timing, natural history, and molecular genetics of pediatric leukemia in general. We reviewed both the older literature and more recent molecular biologic studies that have uncovered the basis of concordance of leukemia. Molecular markers of clonality, including unique, genomic fusion gene sequences, have provided unequivocal evidence that twin pairs of leukemia have a common clonal origin. The only plausible basis for this, first suggested more than 40 years ago, is that following initiation of leukemia in one twin fetus, clonal progeny spread to the co-twin via vascular anastomoses within a single, monochorionic placenta. This explanation has been endorsed by the identification of clonotypic gene fusion sequences in archived neonatal blood spots of individuals who subsequently developed leukemia. These analyses of twin leukemias have thrown considerable light on the natural history of disease. They reveal a frequent prenatal origin and an early or initiating role for chromosome translocations. Further, they provide evidence for a variable and often protracted latency and the need, in childhood acute lymphoblastic leukemia (ALL)/acute myeloblastic leukemia (AML), for further postnatal exposures and/or genetic events to produce clinical disease. We argue that these insights provide a very useful framework for attempts to understand etiologic mechanisms.
    Blood 11/2003; 102(7):2321-33. DOI:10.1182/blood-2002-12-3817 · 10.45 Impact Factor
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    ABSTRACT: To investigate the relationship between birth weight and risk of early age childhood cancer and whether racial differences in birth weight distribution could explain differences in the incidence of cancer in white, Hispanic, and black children. We compared birth weights of 268 children younger than five years old and diagnosed with cancer in the State of Texas in 1995 to the birth weights of 2680 randomly selected, age-matched population-based controls. Birth weight, sex, race/ethnicity, maternal age, smoking status, parity, and gestational age information was ascertained from the birth certificates. Logistic regression analyses were performed to evaluate the association between high birth weight (>4,000 g) and occurrence of childhood cancer. Increased odds ratios (OR) were found for "total cancer cases" (OR 1.4, 95% CI 0.9-2.1), "leukemia cases" (OR 1.7, 95% CI 0.9-3.0) and "acute lymphoblastic leukemia (ALL) cases" (OR 2.2, 95% CI 1.2-4.1). Increased ORs in the former two groups were shown to be due to ALL cases. Including the race/ethnicity variable in the regression model did not affect the ORs. Compared to newborns who weighed between 2500 and 4000 g at birth, children who weighed >4,000 g had an increased risk of developing childhood ALL during the first five years of life. Birth weight differences does not explain the sequence of childhood cancer incidence by race/ethnicity.
    Cancer Causes and Control 09/2002; 13(7):595-602. DOI:10.1023/A:1019555912243 · 2.74 Impact Factor
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    ABSTRACT: Most medications exhibit wide interpatient variability in their efficacy and toxicity. For many medications, these interindividual differences result in part from polymorphisms in genes encoding drug-metabolizing enzymes, drug transporters, and/or drug targets (eg, receptors, enzymes). Pharmacogenomics is a burgeoning field aimed at elucidating the genetic basis of differences in drug efficacy and toxicity, using genome-wide approaches to identify the network of genes that govern an individual's response to drug therapy. For some genetic polymorphisms, such as thiopurine S-methyltransferase (TPMT), monogenic traits have a marked effect on the pharmacokinetics of medications, such that individuals who inherit an enzyme deficiency must be treated with markedly different doses of the affected medications (eg, 5-10% of the standard thiopurine dose). This review uses the TPMT polymorphism and thiopurine therapy (eg, azathioprine, mercaptopurine) to illustrate the potential of pharmacogenomics to elucidate genetic determinants of drug response, and optimize the selection of drug therapy for individual patients.
    Therapeutic Drug Monitoring 05/2004; 26(2):186-91. DOI:10.1097/00007691-200404000-00018 · 2.38 Impact Factor


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