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  1 / 19647 MEDLINE  
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[PMID]:27773462
[Au] Autor:Yu L; Li L; Medeiros LJ; Young KH
[Ad] Endereço:Department of Hematopathology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA; Department of Hematology, The Second Affiliated Hospital of Nanchang University, Nanchang, China.
[Ti] Título:NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms.
[So] Source:Blood Rev;31(2):77-92, 2017 Mar.
[Is] ISSN:1532-1681
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The NF-κB pathway, a critical regulator of apoptosis, plays a key role in many normal cellular functions. Genetic alterations and other mechanisms leading to constitutive activation of the NF-κB pathway contribute to cancer development, progression and therapy resistance by activation of downstream anti-apoptotic pathways, unfavorable microenvironment interactions, and gene dysregulation. Not surprisingly, given its importance to normal and cancer cell function, the NF-κB pathway has emerged as a target for therapy. In the review, we present the physiologic role of the NF-κB pathway and recent advances in better understanding of the pathologic roles of the NF-κB pathway in major types of lymphoid neoplasms. We also provide an update of clinical trials that use NF-κB pathway inhibitors. These trials are exploring the clinical efficiency of combining NF-κB pathway inhibitors with various agents that target diverse mechanisms of action with the goal being to optimize novel therapeutic opportunities for targeting oncogenic pathways to eradicate cancer cells.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Leucemia Linfoide/tratamento farmacológico
Leucemia Linfoide/metabolismo
Linfoma/tratamento farmacológico
Linfoma/metabolismo
Terapia de Alvo Molecular
NF-kappa B/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Biomarcadores Tumorais
Ensaios Clínicos como Assunto
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Leucemia Linfoide/diagnóstico
Leucemia Linfoide/etiologia
Tecido Linfoide/efeitos dos fármacos
Tecido Linfoide/metabolismo
Tecido Linfoide/patologia
Linfoma/diagnóstico
Linfoma/etiologia
Mutação
Resultado do Tratamento
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (NF-kappa B)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  2 / 19647 MEDLINE  
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[PMID]:28982856
[Au] Autor:Tarrini G; Ciabatti E; Pacini S; Galimberti S; Petrini I
[Ad] Endereço:Section of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
[Ti] Título: Mutations Are Common in Thymic Epithelial Tumors But Not in Hematological Malignancies.
[So] Source:Anticancer Res;37(10):5459-5462, 2017 10.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Mutation of general transcription factor IIi (GTF2I) (chromosome 7 c.74146970T>A) is common in thymic epithelial tumors and is a candidate driver aberration for cancer growth. To our knowledge, this mutation has not been described in other diseases. We evaluated the presence of GTF2I mutation in hematological malignancies. MATERIALS AND METHODS: We sequenced samples from 31 patients with acute leukemia, 29 with chronic leukemia and 12 with myelodysplastic syndrome. The genomic fragment of exon 15 containing the hotspot of mutation was amplified using polymerase chain reaction (PCR) and sequenced. RESULTS: We did not identify any GTF2I mutation in patients with hematological malignancies. CONCLUSION: Even though our sample size was limited, our data and reports from the literature suggest that GTF2I mutation is not present or is uncommon in these diseases.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Leucemia/genética
Mutação
Síndromes Mielodisplásicas/genética
Neoplasias Epiteliais e Glandulares/genética
Neoplasias do Timo/genética
Fatores de Transcrição TFII/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Análise Mutacional de DNA
Predisposição Genética para Doença
Seres Humanos
Leucemia/patologia
Leucemia Linfoide/genética
Leucemia Linfoide/patologia
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Leucemia Mieloide Aguda/genética
Leucemia Mieloide Aguda/patologia
Meia-Idade
Síndromes Mielodisplásicas/patologia
Neoplasias Epiteliais e Glandulares/patologia
Fenótipo
Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
Neoplasias do Timo/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (GTF2I protein, human); 0 (Transcription Factors, TFII)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171007
[St] Status:MEDLINE


  3 / 19647 MEDLINE  
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[PMID]:28659300
[Au] Autor:Bertrand KA; Giovannucci E; Rosner BA; Zhang SM; Laden F; Birmann BM
[Ad] Endereço:Slone Epidemiology Center, Boston University, Boston, MA; kab15@bu.edu.
[Ti] Título:Dietary fat intake and risk of non-Hodgkin lymphoma in 2 large prospective cohorts.
[So] Source:Am J Clin Nutr;106(2):650-656, 2017 Aug.
[Is] ISSN:1938-3207
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dietary fat intake may contribute to non-Hodgkin lymphoma (NHL) pathogenesis by influencing carcinogen exposure or through immune modulation. We aimed to evaluate NHL risk associated with total and specific dietary fat intake. We evaluated associations within the Nurses' Health Study (NHS) ( = 88,598) and the Health Professionals Follow-Up Study (HPFS) ( = 47,531) using repeated validated dietary assessments. We confirmed 1802 incident NHL diagnoses through 2010. Using multivariable Cox proportional hazards models, we estimated hazard ratios (HRs) for all NHL and common subtypes associated with a 1-SD increase in cumulative mean intakes of total, animal, saturated, and vegetable fats and marine fatty acids. We pooled sex-specific HRs using random-effects meta-analysis. Over 24-30 y of follow-up, neither total nor specific dietary fats were significantly associated with NHL risk overall. Higher total, animal, and saturated fat intakes were positively associated with the risk of the chronic lymphocytic leukemia/small lymphocytic lymphoma subtype among women only (253 cases; -trend ≤ 0.05), driven by strong associations during 1980-1994. From baseline through 1994, among women and men combined, total fat intake was borderline-significantly positively associated with NHL overall (pooled HR per SD: 1.13; 95% CI: 0.99, 1.29) and was significantly associated with diffuse large B cell lymphoma (pooled HR per SD: 1.47; 95% CI: 1.06, 2.05), with similar trends for animal and saturated fat intake. For women only, fat was significantly positively associated with all NHL. In contrast, during 1994-2010, there was little evidence for associations of dietary fat intake with NHL overall or by subtype. Previous observations of an increased risk of NHL associated with intakes of total, animal, saturated, and fat with 14 y of follow-up did not persist with longer follow-up.
[Mh] Termos MeSH primário: Dieta
Gorduras na Dieta/efeitos adversos
Comportamento Alimentar
Linfoma não Hodgkin/etiologia
Ácidos Graxos Trans/efeitos adversos
[Mh] Termos MeSH secundário: Adulto
Animais
Ingestão de Energia
Ácidos Graxos/efeitos adversos
Feminino
Seguimentos
Seres Humanos
Leucemia Linfoide/etiologia
Linfoma de Células B/etiologia
Masculino
Meia-Idade
Modelos de Riscos Proporcionais
Estudos Prospectivos
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dietary Fats); 0 (Fatty Acids); 0 (Trans Fatty Acids)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170825
[Lr] Data última revisão:
170825
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.3945/ajcn.117.155010


  4 / 19647 MEDLINE  
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[PMID]:28430788
[Au] Autor:Ye X; Torabi M; Lix LM; Mahmud SM
[Ad] Endereço:Department of Community Health Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
[Ti] Título:Time and spatial trends in lymphoid leukemia and lymphoma incidence and survival among children and adolescents in Manitoba, Canada: 1984-2013.
[So] Source:PLoS One;12(4):e0175701, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To test for time and spatial trends in lymphoid malignancies, including lymphoid leukemia (LL), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL), in children and adolescents in the province of Manitoba, Canada. METHODS: Incident cases diagnosed between 1984 and 2013 were identified from the Manitoba Cancer Registry. We assessed time trends in age-standardized incidence rates using joinpoint regression and in 5-year relative survival using Poisson regression model. Kulldorff's scan method was used to assess spatial variation and clustering. RESULTS: Age-standardized incidence rates (per million person-years) in males and females were 34.0 (95% confidence interval [CI] 28.9-39.1) and 26.2 (95% CI 21.5-30.7) for LL, 10.5 (95% CI 7.7-13.3) and 12.5 (95% CI 9.4-15.7) for HL, 12.5 (95% CI 9.3-15.4) and 7.7 (95% CI 5.2-10.2) for NHL (except for Burkitt lymphomas), and 3.2 (95% CI 1.6-4.7) and 1.5 (95% CI 0.4-2.5) for Burkitt lymphomas. Age- and sex- standardized LL incidence rate increased 1.4% (95% CI 0.3%-2.5%) per year, while the changes for HL and NHL incidence rates were not statistically significant. There were geographic differences in age-standardized incidence rates for LL, HL, and NHL and spatial clusters were detected in southern part of the province. Five-year relative survival has improved over time and there was no difference between rural and urban areas. CONCLUSIONS: Lymphoid leukemia incidence rate increased over time and varied by geographic area. Further research should examine the factors contributing to these trends.
[Mh] Termos MeSH primário: Leucemia Linfoide/epidemiologia
Linfoma/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Criança
Pré-Escolar
Feminino
Seres Humanos
Incidência
Masculino
Manitoba/epidemiologia
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170422
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175701


  5 / 19647 MEDLINE  
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[PMID]:28281408
[Au] Autor:Zhou DM; Xu YX; Zhang LY; Sun Y; Wang ZY; Yuan YQ; Fu JX
[Ad] Endereço:a Department of Hematology , The Second Affiliated Hospital of Soochow University , Suzhou , China.
[Ti] Título:The role of follicular T helper cells in patients with malignant lymphoid disease.
[So] Source:Hematology;22(7):412-418, 2017 Aug.
[Is] ISSN:1607-8454
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: To investigate the dynamic change of follicular T helper cells (T ) in patients with malignant lymphoid disease (MLD) and to explore its clinical significance. METHODS: The dynamic change of T cells, ICOS - and PD-1 T cells at pretreatment and different treatment periods was determined by flow cytometry in 85 MLD patients. Concentration of interleukin 21 (IL-21) was evaluated by ELISA, and the correlation between clinical prognosis and the ratio of T cells was analyzed. RESULTS: Significantly increased ICOS - and PD-1 T cells were found in MLD patients at pretreatment compared to healthy controls. Decreased or even close to normal levels of ICOS - and PD-1 T cells were found at the end of treatment. However, in the patients with progressive disease, high levels of ICOS - and PD-1 T cells were found. Moreover, a significantly increased plasma IL-21 level was found in MLD patients. Negative correlation was found between the level of ICOS -, PD-1 T cells, as well as IL-21 and the prognosis of MLD. CONCLUSIONS: Significantly increased T cell ratios were found in patients with MLD, and decreased T cells ratios could be expected in those treatment-effective patients, which could be used as the therapeutic efficacy index.
[Mh] Termos MeSH primário: Leucemia Linfoide/metabolismo
Linfoma/metabolismo
Linfócitos T Auxiliares-Indutores/metabolismo
[Mh] Termos MeSH secundário: Cariótipo Anormal
Adulto
Idoso
Biomarcadores
Estudos de Casos e Controles
Citocinas/sangue
Feminino
Seres Humanos
Imunofenotipagem
Mediadores da Inflamação/sangue
Leucemia Linfoide/genética
Leucemia Linfoide/mortalidade
Leucemia Linfoide/terapia
Contagem de Linfócitos
Linfoma/genética
Linfoma/terapia
Masculino
Meia-Idade
Mutação
Prognóstico
Indução de Remissão
Linfócitos T Auxiliares-Indutores/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Cytokines); 0 (Inflammation Mediators)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171009
[Lr] Data última revisão:
171009
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1080/10245332.2017.1300623


  6 / 19647 MEDLINE  
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[PMID]:28260095
[Au] Autor:Kim YI; Park SW; Kwon HS; Yang HS; Cho SY; Kim YJ; Lee HJ
[Ad] Endereço:Medical Science Research Institute, Kyung Hee University Medical Center, Seoul 02447, Republic of Korea.
[Ti] Título:Inhibin-α gene mutations and mRNA levels in human lymphoid and myeloid leukemia cells.
[So] Source:Int J Oncol;50(4):1403-1412, 2017 Apr.
[Is] ISSN:1791-2423
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:The inhibin-α gene was identified as a tumor suppressor gene in the gonads and adrenal glands by functional studies using knockout mice. Methylation of CpG sites within the regulatory regions of tumor suppressor gene is frequently associated with their transcriptional silencing. We investigated epigenetic modifications, changes in loss of heterozygosity (LOH), and mutation of the inhibin-α gene, and regulation of transcriptional expression in response to inhibitors of DNA methylation (5-aza-2'-deoxycytidine, 5-AzaC) in human lymphoid (Jurkat, Molt-4, Raji, and IM-9) and myeloid (HL-60, Kasumi-1, and K562) leukemia cells. The inhibin-α promoter was hypermethylated in lymphoid (Molt-4 and Raji) and myeloid (HL-60 and Kasumi-1) leukemia cells. Inhibin-α gene mutations differed significantly between lymphoid (heterozygote) and myeloid (homozygote) leukemia cells. LOH in the inhibin-α gene was detected in lymphoid and myeloid leukemia cells, with the exception of Jurkat cells. Treatment with 5-AzaC, a demethylating agent, resulted in increased inhibin-α mRNA and protein levels in most of the cell lines. Also, 5-AzaC treatment inhibited cell proliferation and induced apoptosis. Taken together, our results reveal that the inhibin-α gene is transcriptionally silenced in human leukemia cells and that reactivation is suppressed by a demethylating agent. In addition, mutations in, and expression levels of, the inhibin-α gene differed between human lymphoid and myeloid leukemia cells.
[Mh] Termos MeSH primário: Metilação de DNA
Epigênese Genética
Regulação Neoplásica da Expressão Gênica
Inibinas/genética
Leucemia Linfoide/genética
Leucemia Mieloide/genética
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Azacitidina/análogos & derivados
Azacitidina/farmacologia
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Ilhas de CpG/genética
Metilação de DNA/efeitos dos fármacos
Inibidores Enzimáticos/farmacologia
Inativação Gênica
Seres Humanos
Perda de Heterozigosidade
Mutação
Regiões Promotoras Genéticas
RNA Mensageiro/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 0 (RNA, Messenger); 0 (inhibin-alpha subunit); 57285-09-3 (Inhibins); 776B62CQ27 (decitabine); M801H13NRU (Azacitidine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170306
[St] Status:MEDLINE
[do] DOI:10.3892/ijo.2017.3895


  7 / 19647 MEDLINE  
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[PMID]:28239786
[Au] Autor:Dolgikh TY; Domnikova NP; Tornuev YV; Vinogradova EV; Krinitsyna YM
[Ad] Endereço:Institute of Molecular Pathology and Pathomorphology, Novosibirsk, Russia. pathol@inbox.ru.
[Ti] Título:Incidence of Myelofibrosis in Chronic Myeloid Leukemia, Multiple Myeloma, and Chronic Lymphoid Leukemia during Various Phases of Diseases.
[So] Source:Bull Exp Biol Med;162(4):483-487, 2017 Feb.
[Is] ISSN:1573-8221
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pathomorphological study of trephinobiopsy specimens from 129 patients with lymphoproliferative and myeloproliferative diseases was carried out over the course of chemotherapy. Combinations of initial and manifest myelofibrosis (loose network of reticulin fibers and extensive network of reticulin and collagen fibers, respectively) predominated at the debut of chronic myeloid leukemia, chronic lymphoid leukemia, and multiple myeloma. Manifest myelofibrosis was detected in patients with chronic myeloid leukemia without hematological response (failure of normalization of hematological values) and in patients with progressing and relapsing multiple myeloma. Combinations of foci of initial and manifest myelofibrosis were most incident in patients with progressing and relapsing chronic lymphoid leukemia. The incidence of myelofibrosis was higher in patients with multiple myeloma and chronic lymphoid leukemia progression and relapses and in patients with chronic myeloid leukemia without hematological response than at the disease debut and in case of response to chemotherapy. The response to chemotherapy in patients with chronic myeloid leukemia and chronic lymphoid leukemia was associated with a decrease in the incidence of myelofibrosis. In patients with multiple myeloma responding to chemotherapy, the incidence of myelofibrosis did not change in comparison with the disease debut.
[Mh] Termos MeSH primário: Medula Óssea/patologia
Leucemia Linfoide/complicações
Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações
Mieloma Múltiplo/complicações
Mielofibrose Primária/complicações
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Medula Óssea/efeitos dos fármacos
Doença Crônica
Progressão da Doença
Feminino
Seres Humanos
Leucemia Linfoide/diagnóstico
Leucemia Linfoide/tratamento farmacológico
Leucemia Linfoide/patologia
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico
Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico
Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia
Masculino
Meia-Idade
Mieloma Múltiplo/diagnóstico
Mieloma Múltiplo/tratamento farmacológico
Mieloma Múltiplo/patologia
Estadiamento de Neoplasias
Mielofibrose Primária/diagnóstico
Mielofibrose Primária/tratamento farmacológico
Mielofibrose Primária/patologia
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170315
[Lr] Data última revisão:
170315
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE
[do] DOI:10.1007/s10517-017-3645-x


  8 / 19647 MEDLINE  
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[PMID]:27297832
[Au] Autor:AlGain M; Damade R; Aucouturier F; Rivet J; Jachiet M; Malphettes M; Hickman G; Szalat R; Saussine A; de Masson A; Petit A; Rybojad M; Bagot M; Arnulf B; Bouaziz JD
[Ad] Endereço:Department of Dermatology, Saint-Louis Hospital, Paris, France.
[Ti] Título:Catastrophic cryofibrinogenaemia associated with chronic lymphocytic leukaemia and salvage therapy using plasmapheresis and cyclophosphamide.
[So] Source:J Eur Acad Dermatol Venereol;31(1):e38-e39, 2017 Jan.
[Is] ISSN:1468-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Crioglobulinemia/etiologia
Ciclofosfamida/uso terapêutico
Leucemia Linfoide/congênito
Plasmaferese
Terapia de Salvação/métodos
[Mh] Termos MeSH secundário: Idoso
Crioglobulinemia/terapia
Feminino
Seres Humanos
[Pt] Tipo de publicação:CASE REPORTS; LETTER
[Nm] Nome de substância:
8N3DW7272P (Cyclophosphamide)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170720
[Lr] Data última revisão:
170720
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160615
[St] Status:MEDLINE
[do] DOI:10.1111/jdv.13628


  9 / 19647 MEDLINE  
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[PMID]:28107067
[Ti] Título:What Is Your Diagnosis?
[So] Source:J Avian Med Surg;30(4):405-408, 2016 Dec.
[Is] ISSN:1082-6742
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Doenças das Aves/diagnóstico
Leucemia Linfoide/veterinária
Estrigiformes
[Mh] Termos MeSH secundário: Animais
Feminino
Leucemia Linfoide/diagnóstico
Leucemia Linfoide/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170619
[Lr] Data última revisão:
170619
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170121
[St] Status:MEDLINE
[do] DOI:10.1647/2014-045


  10 / 19647 MEDLINE  
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[PMID]:27959900
[Au] Autor:Kim JA; Hwang B; Park SN; Huh S; Im K; Choi S; Chung HY; Huh J; Seo EJ; Lee JH; Bang D; Lee DS
[Ad] Endereço:Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
[Ti] Título:Genomic Profile of Chronic Lymphocytic Leukemia in Korea Identified by Targeted Sequencing.
[So] Source:PLoS One;11(12):e0167641, 2016.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chronic lymphocytic leukemia (CLL) is extremely rare in Asian countries and there has been one report on genetic changes for 5 genes (TP53, SF3B1, NOTCH1, MYD88, and BIRC3) by Sanger sequencing in Chinese CLL. Yet studies of CLL in Asian countries using Next generation sequencing have not been reported. We aimed to characterize the genomic profiles of Korean CLL and to find out ethnic differences in somatic mutations with prognostic implications. We performed targeted sequencing for 87 gene panel using next-generation sequencing along with G-banding and fluorescent in situ hybridization (FISH) for chromosome 12, 13q14.3 deletion, 17p13 deletion, and 11q22 deletion. Overall, 36 out of 48 patients (75%) harbored at least one mutation and mean number of mutation per patient was 1.6 (range 0-6). Aberrant karyotypes were observed in 30.4% by G-banding and 66.7% by FISH. Most recurrent mutation (>10% frequency) was ATM (20.8%) followed by TP53 (14.6%), SF3B1 (10.4%), KLHL6 (8.3%), and BCOR (6.25%). Mutations of MYD88 was associated with moderate adverse prognosis by multiple comparisons (P = 0.055). Mutation frequencies of MYD88, SAMHD1, EGR2, DDX3X, ZMYM3, and MED12 showed similar incidence with Caucasians, while mutation frequencies of ATM, TP53, KLHL6, BCOR and CDKN2A tend to be higher in Koreans than in Caucasians. Especially, ATM mutation showed 1.5 fold higher incidence than Caucasians, while mutation frequencies of SF3B1, NOTCH1, CHD2 and POT1 tend to be lower in Koreans than in Caucasians. However, mutation frequencies between Caucasians and Koreans were not significantly different statistically, probably due to low number of patients. Collectively, mutational profile and adverse prognostic genes in Korean CLL were different from those of Caucasians, suggesting an ethnic difference, while profile of cytogenetic aberrations was similar to those of Caucasians.
[Mh] Termos MeSH primário: Loci Gênicos
Genoma Humano
Leucemia Linfoide/genética
Mutação
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Grupo com Ancestrais do Continente Asiático
Estudos de Casos e Controles
Aberrações Cromossômicas
Grupo com Ancestrais do Continente Europeu
Feminino
Seres Humanos
Leucemia Linfoide/etnologia
Leucemia Linfoide/patologia
Masculino
Meia-Idade
Taxa de Mutação
República da Coreia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170629
[Lr] Data última revisão:
170629
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0167641



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