Inactivation of the p15 gene in children with acute lymphoblastic leukemia

CONTEXT: Tumor suppressor genes act on the control of cell cycle progression. In pediatric neoplasias, some of these genes may be considered to be markers for diagnosis or relapse, thus probably representing prognostic indicators. OBJECTIVE: To study the inactivation of the p15 gene in children with acute lymphoblastic leukemia. TYPE OF STUDY: Retrospective study. SETTING: Laboratory of Molecular Biology, Department of Pediatrics, Faculdade de Medicina de Ribeiräo Preto, Universidade de Säo Paulo. PARTICIPANTS: Eighty-three children and adolescents with acute lymphoblastic leukemia were studied, with the examination of 83 bone marrow samples obtained at diagnosis, four obtained also during relapse, and two cerebrospinal fluid samples obtained from two cases of isolated relapse in the central nervous system. MAIN MEASUREMENTS: Homologous deletion of the p15 gene by multiplex polymerase chain reaction, and screening for point mutations by polymerase chain reaction/single-strand conformational polymorphism. RESULTS: Deletion of exon 2 of the p15 gene was observed in 15 children, including one case in which deletion was only verified during isolated central nervous system relapse. No case of exon 1 deletion, or that was suggestive of point mutations, was observed and no association between p15 gene inactivation and classic risk factors was established. CONCLUSION: According to the literature, inactivation of the p15 gene by deletion of exon 2 in acute lymphoblastic leukemia found in the population studied would be considered to be a molecular marker for diagnosis or relapse. However, no correlation between p15 gene deletion and clinical prognostic indicators was observed

Analysis of p16 gene mutations and deletions in childhood acute lymphoblastic leukemias

CONTEXT: The p16 tumor suppressor gene encodes a cyclin-dependent kinase 4 inhibitor that blocks cell division during the G1 phase of the cell cycle. Alterations in this gene have been reported for various neoplasia types, including acute lymphoblastic leukemias (ALL), especially T-cell acute lymphoblastic leukemias (ALL). OBJECTIVE: To determine probable alterations in the p16 gene in children with acute lymphoblastic leukemias using the polymerase chain reaction (PCR) and direct DNA sequencing and also to analyze event-free survival (EFS). DESIGN: Retrospective study. SETTING: Department of Child Care and Pediatrics, Faculty of Medicine of Ribeirão Preto, Universidade Federal de São Paulo. PARTICIPANTS: Fifty-six children with ALL (mean age 4 years). Forty (71.43 percent) had B-cell and 12 (21.43 percent) had T-cell ALL; 4 (7.1 percent) were biphenotypic. SAMPLE: DNA samples were extracted from bone marrow upon diagnosis and/or relapse. In 2 T-cell cases, DNA from cerebrospinal fluid (CSF) was analyzed. MAIN MEASUREMENTS: Deletions or nucleotide substitutions in exons 1, 2 and 3 of the p16 gene were determined by PCR and nucleotide sequencing. Event-free survival was determined by the Kaplan-Meyer and log-rank test for patients carrying normal and altered p16. RESULTS: Deletions in exon 3 were observed in five cases. Abnormal migration in PCR was observed in seven cases for exon 1, six for exon 2, and five for exon 3. Mutations in exon 1 were confirmed by direct DNA sequencing in four cases and in exon 2 in two cases. The Kaplan-Meyer survival curves and the log-rank test showed no significant differences in 5-year EFS between children with normal or altered p16, or between patients with B-ALL carrying normal or altered p16 gene. Patients with T-ALL could not be evaluated via Kaplan-Meier due to the small number of cases. CONCLUSIONS: Our results, particularly regarding deletion frequency, agree with others suggesting that deletions in the p16 are initial events in leukemia genesis. The small number of samples did not allow stablishment of correlation between childhood ALL and the p16 point mutations found in our study. Kaplan-Meier analysis revealed no significant correlation between EFS and alterations in ALL. The p16 alterations frequency observed for B and T-ALL agreed with reports from other centers

Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patientsÆ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeiräo Preto, University of Säo Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH) for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9 percent). There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1 percent versus 26.1 percent), presence of CALLA+ (81.2 percent versus 80 percent) or risk group (62.5 percent versus 60 percent). Disease-free survival was similar in both groups, with no significant difference (p: 0.7695). CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9 percent of the patients may be important for the study and monitoring of minimal residual disease

Analysis of the p53 gene by PCR-SSCP in ten cases of WilmsÆ tumor

CONTEXT: Mutations of the p53 tumor suppressor gene are the most frequent alterations observed in human neoplasias affecting adults. In pediatric oncology, however, they have seldom been identified. WilmsÆ tumor is a renal neoplasia commonly occurring in children and is associated with mutations of the WT1 gene. The correlation between WilmsÆ tumor and alterations of the p53 gene has not been well established, with a low frequency of mutations having been reported in this type of tumor. Mutation may be associated with advanced stage disease and unfavorable histology. OBJECTIVE: To screen for mutations of the p53 gene by the PCR-SSCP method and DNA sequencing in cases of WilmsÆ tumor sug-gestive of mutation. DESIGN: Case Report. CASE REPORT: Evaluations of exons 5-9 of the p53 gene in DNA samples extracted by PCR-SSCP from 10 WilmsÆ tumors in children at different stages, and DNA sequencing. Changes in SSCP analy-sis were observed in exon 8 in two samples. The probable muta-tions were not confirmed by DNA sequencing. The absence of point mutations in p53 gene observed in the 10 samples of WilmsÆ tumor studied agrees with literature data, with DNA sequencing being of fundamental importance for the confirmation of possible mutations

Estudo citogenético de leucemia näo-linfóide aguda da infância: análise de doze casos / Cytogenetic study of acute nonlymphoid childhood leukemia. Analysis of 12 cases

Os autores analisam citigeneticamente doze caos de leucemia näo-linfóide aguda da infância (LNLA), objetivando estabelecer correlaçöes entre alteraçöes cromossômicas, evoluçäo e progressäo da doença. 91,66 por cento dos casos exibiam anomalias. Dois pacientes com classificaçäo FAB M1 e M2 apresentaram translocaçäo t(8;21), associada à monossomia do X e à trissomia desse cromossomo, mais alteraçäo do 7, respectivamente. Ambos faleceram, o primeiro após transplante de medula óssea com recidiva da doença e o segundo com septicemia, confirmando o caráter agerssivo dessa translocaçäo quando associada a outras alteraçöes cromossômicas. Em um dos casos a presença de alteraçöes cromossômicas complexas foi fundamental p[ara a confirmaçäo diagnóstica de eritroleucemia. Cinco pacientes exibiram alteraçöes cromossômicas primárias e seis do tipo secundário. No grupo com alteraçöes primárias se encontram os três pacientes vivos livres da doença. No grupo com alteraçöes secundárias, todos foram a óbito, dois por recidiva, dois por resistência à doença e dois por septicemia, após entrar em remissäo...

Analise citogenética de três casos de tumor de wilms da infância / Cytogenetics analysis of 3 cases of children with Wilms tumor

Relatamos os resultados da análise citogenética de três casos de tumor de wilms em crianças. O estudo cromossômico foi realizado a partir do material obtido de cultura de curta duraçäo de células tumorais. observamos alteraçöes numéricas e estruturais, incluindo aberraç 8es estruturais do cromossomo 1 e trissomiais dos cromossomos 8 e 12

Abuso sexual em criancas: uma revisao / Sexual abuse in children a review

O artigo se constitui numa revisao da literatura dos anos 80 sobre abuso sexual na infancia. Visa contribuir com os profissionais de saude que trabalham com criancas e busca instrumenta-los na deteccao e manejo inicial do abuso sexual. Aborda, tambem, situacoes familiares e sociais que cercam oabuso da crianca. Observou-se, na literatura, que o abuso sexual em criancas e muito frequente de 40.000 a 400.000 casos por ano nos Estados Unidos, mas pouco diagnosticado, devido a negacao e a ansiedade que desperta nos profissionais de saude, ao tabu do incesto e a falta de formacao medica orientada para sua identificacao. Isto ocorre pois nem sempre a anamnese e o exame fisico sao claramente sugestivos de abuso sexual. O manejo dos casos deve ser feito por uma equipe multidisciplinar integrada. As recomendacoes do texto baseiam-se na literatura consultada bem como na experiencia dos autores provenientes de atendimentos feitos nainstituicao onde trabalham .

Abuso sexual intrafamiliar: um alerta / Intrafamily sexual abuse: an alert

No artigo, os autores apresentam uma brve revisäo da literatura sobre o abuso sexual intrafamiliar, que é o tipo de abuso sexual mais encontrado, mostrando aspectos familiares envolvidos. Salientam, do mesmo modo, sintomas associados que podem ocorrer em crianças vítimas de abuso sexual e suas conseqüências a longo prazo. Relatam um caso de uma paciente adulta que sofreu abuso sexual na infância. Baseado na experiência clínica dos autores e na literatura, alguns aspectos compreensivos desta paciente e de sua família säo abordados. Por fim, ressaltam a tendência a perpetuaçäo das relaçöes incestuosas de geraçäo a geraçäo. Para possibilitar a interrupçäo deste processo é importante que ocorra uma intervençäo psiquiátrica efetiva

Estudo de alguns fatores na gênese do tabagismo / Some factors in the genesis of smoking

Foram estudados 573 alunos adolescentes com a finalidade de se conhecer os principais motivos pelos quais eles começam a fumar. Nossa amostra foi obtida em dois colégios de Porto Alegre, um deles freqüentado por alunos de classe alta (52,5% dos entrevistados) e outro, por alunos de classe média-baixa (47,5% dos entrevistados), sendo composta por jovens de 12 a 20 anos de idade (16 anos em média). Os principais motivos que incentivaram a adesäo ao hábito de fumar foram: "Curiosidade" (57,3%), "Influência de amigos" (10,5%) e "Auto-afirmaçäo" (6,5%). Observou-se que a maior parte dos estudantes (71,6%) iniciou a fumar na faixa etária dos 12 aos 15 anos. Houve maior prevalência do hábito de fumar entre alunos com familiares fumantes (p<0,01) e no sexo feminino (p<0,01). O nível sócio-econômico näo demonstrou relaçäo significativa com história de tabagismo

A fisiatria respiratória em pediatria: aspectos práticos / The respiratory physical therapy in pediatrics: practical aspects

Visando um enfoque prático, os autores revisam as condutas básicas de fisiatria respiratória em Pediatria, assim como as técnicas fisiátricas mais utilizadas, as suas indicaçöes e as suas contra-indicaçöes. Uma vez que a Fisiatria é indicada em grande número de disfunçöes respiratórias em crianças especialmente nos recém-nascidos, é fundamental que o médico, principalmente o pediatra, tenha conhecimentos de fisiatria respiratória, a fim de indicá-la e de orientar os terapeutas corretamente