RESUMO
AIM: To study distribution of some karyotype variants among patients of different age with acute myeloid leukemia (AML). MATERIAL AND METHODS: Distribution of balanced, normal, unbalanced, complex and monosomic karyotype among 244 patients with de novo AML in age groups 16-20, 21-30, 31-40, 41-50, 51-60, 61 and older was analysed. RESULTS: There is difference in frequency of balanced and complex karyotype in patients under and over 60 years. Number of AML patients with balanced aberrations including favourable variants t(8;21), t(15;17) and inv(16) falls after 60 years of age (6.7% versus 15.0% in patients aged 16-20 years; p < 0.001), while a complex karyotype occurs more frequently in AML patients at the age of 61 and older (56.8% versus 2.7% in the group 16-20 years; p < 0.001). With age, more frequently detected is the most unfavourable monosomic karyotype with aberrations similar to those in myelodysplastic syndrome (57.1% in patients aged 16-60 years and in 80.0% in the group of 61 years of age and over). CONCLUSION: Age-specific karyotype features detected may be explained by different biological mechanisms involved in leukosogenesis in young and elderly AML patients.
Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Densitometry of cosmonauts following long-duration missions shows reduction of bone mineral density (BMD). On the average, post-flight BMD remains within the normal range and the broad variability of individual BMD values sometimes is qualified as local osteopenia. Individual reactions are typed by similarity of amount and rate of BMD loss. At present, analysis of functionally significant polymorphism of bone metabolism genes is the most effective instrument for diagnostics of susceptibility to osteopenia and osteoporosis. The investigation was aimed to analyze polymorphism of genes of vitamin-D and (VDR) and calcitonin (CALCR) receptors, and of collagen-1 alpha-1-chain (Col1a-1) in candidate cosmonauts and cosmonauts returned from 5 to 7-mo. missions. According to the results of analysis, in the majority of cosmonauts rapid BMD loss correlated with TT genotype by VDR gene but not with genotypes Tt and tt and associated with carriage of incomplete s-allele in the Col1a1 gene. Yet, in several instances high BMD loss rates were personified with carriers of VDR gene alleles (homo- and heterozygote states--tt and Tt) and heterozygote by Col1a1 gene (Ss).
Assuntos
Densidade Óssea/genética , Doenças Ósseas Metabólicas/genética , Colágeno Tipo I/genética , DNA/genética , Polimorfismo Genético , Receptores da Calcitonina/genética , Receptores de Calcitriol/genética , Astronautas , Doenças Ósseas Metabólicas/metabolismo , Colágeno Tipo I/metabolismo , Cadeia alfa 1 do Colágeno Tipo I , Seguimentos , Humanos , Reação em Cadeia da Polimerase , Receptores da Calcitonina/metabolismo , Receptores de Calcitriol/metabolismo , Estudos Retrospectivos , Fatores de RiscoRESUMO
AIM: To estimate the extent of FLT3 and NPM1 gene mutations and the impact of mutations of FLT3-ITD on the survival of patients with acute myeloid leukemias (AML). MATERIALS AND METHODS: The nucleus-containing cells of bone marrow and blood were studied in 43 patients with AML. Polymerase chain reaction analysis of total genomic DNA was applied. RESULTS: Mutations of FLT3-ITD, FLT3-TDK, and the NPM1 gene were found in 16 (37.2%) patients. A total of 19 mutations were revealed. There were 8 mutations of FLT3-ITD, 5 of FLT3-TKD, and 6 in the NPM1 gene. Single damages to genes were detected in 13 patients: FLT3-ITD in 6 (13.9%), FLT3-TKD in 4 (9.3%), and NPM1 in 3 (7%). Three (7%) patients exhibited 2 mutations simultaneously: in the NPM1 and FLT3-ITD in 2 (4.7%) and in the NPM1 gene and FLT3-TKD in 1 (2.3%). In AML patients with a normal karyotype and the FLT3-ITD-/NPM1 and FLT3-ITD+/ NPM-T genotypes, median overall survival was 17.3 versus 8 months (p = 0.069); and event-free survival (EFS) was 11 versus 5 months (p = 0.026). Univariate analysis established the negative impact of FLT3-1TD mutation on EFS. CONCLUSION: The findings allow AML patients with a normal karyotype and the FLT3-ITD-/NPM-genotypes to be identified as a poor prognosis group.
Assuntos
DNA/genética , Predisposição Genética para Doença , Leucemia Mieloide Aguda/genética , Mutação , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Federação Russa/epidemiologia , Taxa de Sobrevida/tendências , Adulto JovemRESUMO
Two FLT3-ITD mutations, one FLT3-TKD) and five NPM1 mutations were detected in 7 patients with de novo myelodysplastic syndrome (MDS) out of 44 cases of MDS and MDS/mixed myeloid diseases. Expression of one of the three investigated mutations was identified: 4 in gene NPM1 (9.1%) and 2--FLT3-ITD (4.5%); simultaneous FLT3-ITD and NPM1 mutation--1 (2.3%); no progression in NPM1 within 9-20 months--3, although with chromosome 7 damage--2. It was suggested that NPM1 mutation without complex karyotype may serve as marker of relatively favorable course.
Assuntos
Doenças da Medula Óssea/genética , Mutação , Síndromes Mielodisplásicas/genética , Proteínas Nucleares/genética , Tirosina Quinase 3 Semelhante a fms/genética , Idoso , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Nucleofosmina , Valor Preditivo dos Testes , Prognóstico , Fatores de TempoAssuntos
Desempenho Atlético/fisiologia , Remodelação Óssea , Osso e Ossos , Absorciometria de Fóton , Adulto , Biomarcadores/análise , Densidade Óssea/fisiologia , Doenças Ósseas Metabólicas/etiologia , Doenças Ósseas Metabólicas/genética , Doenças Ósseas Metabólicas/metabolismo , Remodelação Óssea/genética , Remodelação Óssea/fisiologia , Osso e Ossos/anatomia & histologia , Osso e Ossos/metabolismo , Marcadores Genéticos/genética , Humanos , Tamanho do Órgão/fisiologia , Reação em Cadeia da Polimerase , Polimorfismo Genético , Estresse Fisiológico/sangue , Estresse Fisiológico/metabolismo , Estresse Fisiológico/fisiopatologiaRESUMO
We studied the dependence of climatotherapy effectiveness in patients with chronic heart failure (functional classes 0-II) on Ca(2+)-ATPase, phospholamban, beta1-adrenoceptor, and insulin-like growth factor 1 gene polymorphisms and possible interaction of these genes during the realization of the effect of climatotherapy. The effectiveness of climatotherapy depended on polymorphism of the studied genes; the maximum effect was attained in patients with the GG polymorphism of the Ca(2+)-ATPase gene, GT polymorphism of the phospholamban gene, ArgGly polymorphism of the beta1-adrenoceptor gene, and 19/19 polymorphism of the insulin-like growth factor 1 gene. We demonstrated additive interaction of Ca(2+)-ATPase and beta1-adrenoceptor genes during the realization of the cardiotonic effect of climatotherapy.
Assuntos
Clima , Estâncias para Tratamento de Saúde , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Polimorfismo Genético , Idoso , Proteínas de Ligação ao Cálcio/genética , ATPases Transportadoras de Cálcio/genética , Doença Crônica , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Fator de Crescimento Insulin-Like I/genética , Masculino , Pessoa de Meia-Idade , Receptores Adrenérgicos beta 1/genética , CaminhadaAssuntos
Baixo Débito Cardíaco/genética , Baixo Débito Cardíaco/terapia , Clima , Estâncias para Tratamento de Saúde , Polimorfismo Genético , Proteínas de Ligação ao Cálcio/genética , ATPases Transportadoras de Cálcio/genética , Doença Crônica , Humanos , Fator de Crescimento Insulin-Like I/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático , Resultado do TratamentoRESUMO
Allele frequencies of the G-->T polymorphism at the regulatory region of the Collal gene in the population of the northwestern Russia (control group) and in osteoporotic patients were estimated by the RFLP method based on PCR-mediated site-directed mutagenesis. Three patient groups with radiologically confirmed osteoporosis were examined. Group 1 consisted of 64 patients with severe osteoporosis complicated by fractures (SO); group 2 included 15 children with idiopathic osteoporosis (IO); group 3 consisted of 98 women with postmenopausal osteoporosis developed at the background of estradiol-deficiency state (PMO). The frequency of functionally defective allele s in the control group was 16.7%. It was statistically different from that in the SO patients (48.4%) (P < 0.01) and in the IO children (40%) (P < 0.01). The frequency of allele s in the PMO patients constituted 23.0% and it was similar to that in the control group (P > 0.05). Analysis of the Collal alleles provides early detection of the individuals with hereditary predisposition to osteoporosis and prophylaxis of the disease at the presymptomatic stage.
