RESUMO
OBJECTIVE: to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 genein chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe. METHODS: Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP acci-dent (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups ofpatients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main andalternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). TheIGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data wereanalyzed with the SPSS software package, version 20.0. RESULTS: Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57),did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expressionof B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relativeexpression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01-90.51). The expression of SORL1-Δ2transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmu-tated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene inpatients of the main and the control groups did not differ. CONCLUSIONS: Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients withunmutated IGHV genes can be considered as a negative prognostic marker.
Assuntos
Acidente Nuclear de Chernobyl , Proteínas Relacionadas a Receptor de LDL/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/fisiopatologia , Leucemia Induzida por Radiação/genética , Leucemia Induzida por Radiação/fisiopatologia , Proteínas de Membrana Transportadoras/genética , Adulto , Idoso , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Exposição Ocupacional/efeitos adversos , Exposição à Radiação/efeitos adversos , Liberação Nociva de Radioativos , Transcrição Gênica , UcrâniaRESUMO
OBJECTIVE: to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes inperipheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophedepending on the mutational status of IGHV genes. METHODS: Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV genemutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYCexpression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0. RESULTS: Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1).A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684;p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0-48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlationbetween LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013. CONCLUSIONS: Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the actionof proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression ofa functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL.
Assuntos
Acidente Nuclear de Chernobyl , Genes de Cadeia Pesada de Imunoglobulina , Leucemia Linfocítica Crônica de Células B/genética , Lipase Lipoproteica/genética , Proteínas Proto-Oncogênicas c-myc/genética , Exposição à Radiação/efeitos adversos , Lesões por Radiação/genética , Idoso , Poluentes Radioativos do Ar/efeitos adversos , Socorristas , Feminino , Contaminação Radioativa de Alimentos , Regulação da Expressão Gênica , Humanos , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/imunologia , Leucemia Linfocítica Crônica de Células B/patologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Leucócitos Mononucleares/efeitos da radiação , Lipase Lipoproteica/imunologia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Proteínas Proto-Oncogênicas c-myc/imunologia , Lesões por Radiação/etiologia , Lesões por Radiação/imunologia , Lesões por Radiação/patologia , Radioisótopos , Poluentes Radioativos do Solo/efeitos adversos , UcrâniaRESUMO
OBJECTIVE: to test the method of polymerase chain reaction with following fragments' length restriction to deter mine the rs2124594 polymorphism and to study its contribution in the development of chronic lymphocytic leukemia (CLL) in the post Chornobyl period. METHODS: Genotypes of rs2124594 were determined in 109 patients with CLL of B cell origin including 53 patients irradiated due to the Chornobyl NPP accident. Genotypes distribution among CLL patients was compared with healthy persons of European origin (the 1000 Genomes Project data set was used as a reference). RESULTS: Validity of the tested method was confirmed by direct sequencing. Associations between CLL risks and C allele (OR = 2.37; 95 % CI 1.50-3.73; Ñ = 0.003), CLL risks and CT genotype (OR = 2.10; 95 % CI 1.38-3.21; Ñ = 0.0012) were found. Distributions of rs2124594 genotypes in exposed and non exposed to ionizing radiation CLL patients did not differ. CONCLUSIONS: The association of single nucleotide polymorphisms across the 8q24 chromosome region (positioned at 127180736 and 127183014 near Ñ MYC gene) with CLL risks was confirmed. Modified influence of ionizing radia tion on genetic susceptibility associated with rs2124594 was not found in this pilot study.
Assuntos
Acidente Nuclear de Chernobyl , Genótipo , Leucemia Linfocítica Crônica de Células B/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-myc/genética , Exposição à Radiação/efeitos adversos , Adulto , Idoso , Alelos , Linfócitos B/metabolismo , Linfócitos B/patologia , Estudos de Casos e Controles , Cromossomos Humanos Par 8 , Feminino , Loci Gênicos , Humanos , Leucemia Linfocítica Crônica de Células B/etiologia , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Proto-Oncogênicas c-myc/metabolismo , Radiação Ionizante , RiscoRESUMO
A clinical case of the rituximab («Rituksim¼, «Mabthera¼) use to treat a man affected by the Chornobyl NPP acci dent with malignant resistant form of myasthenia gravis in conjunction with chronic mixed infection by Toxoplasma, Epstein Barr virus, Cytomegalovirus and Herpes simplex virus is described. In the dynamics of two year's observa tion the clinical efficacy of monoclonal antibodies was shown as the main symptoms stabilization and reducing doses of glucocorticoid and anticholinergic therapy. The positive effect was marked in the nearest and remote peri ods. Taking to account the efficacy, safety and good tolerability of rituximab, it is advisable to recommend treat ment for people exposed to ionizing radiation and developing myasthenia associated with chronic mixed infection by Toxoplasma, Epstein Barr, Cytomegalovirus and Herpes simplex virus.
Assuntos
Acidente Nuclear de Chernobyl , Miastenia Gravis/tratamento farmacológico , Exposição à Radiação/efeitos adversos , Rituximab/uso terapêutico , Viroses/tratamento farmacológico , Antivirais/uso terapêutico , Antagonistas Colinérgicos/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/crescimento & desenvolvimento , Cálculos da Dosagem de Medicamento , Quimioterapia Combinada , Glucocorticoides/uso terapêutico , Herpesvirus Humano 4/efeitos dos fármacos , Herpesvirus Humano 4/crescimento & desenvolvimento , Humanos , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/etiologia , Miastenia Gravis/patologia , Doses de Radiação , Simplexvirus/efeitos dos fármacos , Simplexvirus/crescimento & desenvolvimento , Sobreviventes , Resultado do Tratamento , Viroses/etiologia , Viroses/patologiaRESUMO
The article considers the possibility of the use of current infrastructure of specialized population registers of Ukraine to study leukemia and other systemic blood diseases revealed in Chernobyl accident liquidators. Advantage and limitation of such registers in the use are discussed in the article. Ukrainian state register of people who suffered from Chernobyl accident and Ukrainian national cancer registers are the largest population registers in the country, which cover all the territory of Ukraine and contain information on each individual and may serve as source base for epidemiological studies. To solve issues on leukemia and other oncological diseases is recommended to use in complex data of specialized registers of Ukraine. It should be also taken into account necessity of using late registered cases and verifying registered diagnoses.
Assuntos
Acidente Nuclear de Chernobyl , Indicadores Básicos de Saúde , Leucemia , Sistema de Registros , Projetos de Pesquisa , Humanos , Leucemia/epidemiologia , Leucemia/etiologia , Sistema de Registros/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Ucrânia/epidemiologiaRESUMO
The results of proper investigations received under the cytogenetic examination of 225 persons (control groups, Chernobyl liquidators exposed to different radiation doses, oncogematology patients) had been summarized and analyzed. The conclusion concerning possibilities and limitations of FISH technique usage for retrospective biodosimetry of human radiation exposure has been presented.
Assuntos
Acidente Nuclear de Chernobyl , Exposição Ambiental/análise , Hibridização in Situ Fluorescente , Linfócitos/efeitos da radiação , Poluentes Radioativos/análise , Translocação Genética/efeitos da radiação , Adulto , Idoso , Neoplasias Hematológicas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Doses de Radiação , Radiometria/métodos , Estudos Retrospectivos , Ucrânia , Estados UnidosAssuntos
Hematopoese/efeitos da radiação , Células Sanguíneas/fisiologia , Células Sanguíneas/efeitos da radiação , Medula Óssea/patologia , Medula Óssea/efeitos da radiação , Relação Dose-Resposta à Radiação , Feminino , Doenças Hematológicas/sangue , Doenças Hematológicas/etiologia , Hemorragia/sangue , Hemorragia/etiologia , Humanos , Masculino , Centrais Elétricas , Liberação Nociva de Radioativos , Fatores de Tempo , UcrâniaAssuntos
Leucemia Linfocítica Crônica de Células B/terapia , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Humanos , Leucaférese , Leucemia Linfocítica Crônica de Células B/classificação , Prognóstico , Radioterapia/métodos , Indução de RemissãoAssuntos
Hematopoese/efeitos da radiação , Doenças Profissionais/sangue , Centrais Elétricas , Lesões por Radiação/sangue , Liberação Nociva de Radioativos , Doença Aguda , Anemia Aplástica/sangue , Anemia Aplástica/diagnóstico , Anemia Aplástica/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Doenças Profissionais/complicações , Doenças Profissionais/diagnóstico , Lesões por Radiação/complicações , Lesões por Radiação/diagnóstico , Estudos Retrospectivos , Fatores de Tempo , UcrâniaRESUMO
The paper reports on the preliminary experience of treatment of those patients having been the victims to the reactor accident at the Chernobyl NPP as well as of those with acute and chronic leukoses, having received courses of modern cytostatic therapy. The patients were exposed to therapeutic plasmapheresis and enterosorption as part of a complex conventional treatment programme. The conclusion the authors have come to is as follows: enterosorption strikingly reduces manifestations of "cytostatic disease"; the use of plasmapheresis in those persons having been previously exposed to small dose chronic radiation, makes for improvement of clinical and laboratory values but further studies are warranted to determine indications for therapeutic plasmapheresis.
Assuntos
Cuidados Críticos/métodos , Enteroadsorção , Leucemia/terapia , Plasmaferese , Centrais Elétricas , Lesões por Radiação/terapia , Liberação Nociva de Radioativos , Doença Aguda , Adulto , Idoso , Doença Crônica , Terapia Combinada , Feminino , Humanos , Leucemia/complicações , Masculino , Pessoa de Meia-Idade , Indução de Remissão , UcrâniaRESUMO
The peripheral blood of 2200 children (age: from 2 to 16 years) inhabiting the Polessye District of Kiev Province and the city of Kiev 4 years after the Chernobyl atomic station accident was studied. An analysis of results revealed the presence of hematologic changes that may be interpreted as sequels of the effect of ionizing radiation on the body, while other changes may be considered as reactive and may in most cases accompany different somatic diseases of infectious-inflammatory character.