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[PMID]:28456746
[Au] Autor:Carretta M; de Boer B; Jaques J; Antonelli A; Horton SJ; Yuan H; de Bruijn JD; Groen RWJ; Vellenga E; Schuringa JJ
[Ad] Endereço:Department of Experimental Hematology, Cancer Research Centre Groningen, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands.
[Ti] Título:Genetically engineered mesenchymal stromal cells produce IL-3 and TPO to further improve human scaffold-based xenograft models.
[So] Source:Exp Hematol;51:36-46, 2017 07.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Recently, NOD-SCID IL2Rγ (NSG) mice were implanted with human mesenchymal stromal cells (MSCs) in the presence of ceramic scaffolds or Matrigel to mimic the human bone marrow (BM) microenvironment. This approach allowed the engraftment of leukemic samples that failed to engraft in NSG mice without humanized niches and resulted in a better preservation of leukemic stem cell self-renewal properties. To further improve our humanized niche scaffold model, we genetically engineered human MSCs to secrete human interleukin-3 (IL-3) and thrombopoietin (TPO). In vitro, these IL-3- and TPO-producing MSCs were superior in expanding human cord blood (CB) CD34 hematopoietic stem/progenitor cells. MLL-AF9-transduced CB CD34 cells could be transformed efficiently along myeloid or lymphoid lineages on IL-3- and TPO-producing MSCs. In vivo, these genetically engineered MSCs maintained their ability to differentiate into bone, adipocytes, and other stromal components. Upon transplantation of MLL-AF9-transduced CB CD34 cells, acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) developed in engineered scaffolds, in which a significantly higher percentage of myeloid clones was observed in the mouse compartments compared with previous models. Engraftment of primary AML, B-cell ALL, and biphenotypic acute leukemia (BAL) patient samples was also evaluated, and all patient samples could engraft efficiently; the myeloid compartment of the BAL samples was better preserved in the human cytokine scaffold model. In conclusion, we show that we can genetically engineer the ectopic human BM microenvironment in a humanized scaffold xenograft model. This approach will be useful for functional study of the importance of niche factors in normal and malignant human hematopoiesis.
[Mh] Termos MeSH primário: Diferenciação Celular
Engenharia Genética
Interleucina-3
Células Mesenquimais Estromais/metabolismo
Nicho de Células-Tronco
Trombopoetina
Tecidos Suporte/química
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Xenoenxertos
Seres Humanos
Interleucina-3/biossíntese
Interleucina-3/genética
Leucemia Mieloide Aguda/genética
Leucemia Mieloide Aguda/metabolismo
Transplante de Células-Tronco Mesenquimais
Camundongos
Camundongos Endogâmicos NOD
Camundongos SCID
Transplante de Neoplasias
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras B/metabolismo
Trombopoetina/biossíntese
Trombopoetina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (IL3 protein, human); 0 (Interleukin-3); 9014-42-0 (Thrombopoietin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180224
[Lr] Data última revisão:
180224
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:29194562
[Au] Autor:Sutton R; Venn NC; Law T; Boer JM; Trahair TN; Ng A; Den Boer ML; Dissanayake A; Giles JE; Dalzell P; Mayoh C; Barbaric D; Revesz T; Alvaro F; Pieters R; Haber M; Norris MD; Schrappe M; Dalla Pozza L; Marshall GM
[Ad] Endereço:Children's Cancer Institute, Lowy Cancer Research Centre, UNSW, Sydney, Australia.
[Ti] Título:A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children.
[So] Source:Br J Haematol;180(4):550-562, 2018 02.
[Is] ISSN:1365-2141
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P < 0·0001); P2RY8-CRLF2 gene fusion (P < 0·0004); Day 33 MRD>5 × 10 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL.
[Mh] Termos MeSH primário: Deleção Cromossômica
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade
Deleção de Sequência
[Mh] Termos MeSH secundário: Adolescente
Fatores Etários
Biomarcadores Tumorais
Criança
Pré-Escolar
Feminino
Genótipo
Seres Humanos
Lactente
Masculino
Neoplasia Residual/diagnóstico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Prognóstico
Modelos de Riscos Proporcionais
Recidiva
Medição de Risco
Fatores de Risco
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171202
[St] Status:MEDLINE
[do] DOI:10.1111/bjh.15056


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[PMID]:29303717
[Au] Autor:Yaqub F
[Ti] Título:2017: a year in review.
[So] Source:Lancet;390(10114):2753-2754, 2018 12 23.
[Is] ISSN:1474-547X
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Conflitos Armados
Transtornos da Nutrição Infantil/epidemiologia
Cólera/epidemiologia
Epidemias
Direitos Humanos
Imunoterapia Adotiva/métodos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
Refugiados
Delitos Sexuais
Assédio Sexual
[Mh] Termos MeSH secundário: Bangladesh
Pré-Escolar
China
Recessão Econômica
Etiópia/epidemiologia
Abastecimento de Alimentos
Política de Saúde
Seres Humanos
Mianmar
Armas Nucleares
Política
Somália/epidemiologia
Linfócitos T/transplante
Transplante Autólogo
Estados Unidos
Venezuela
Organização Mundial da Saúde
Iêmen/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180117
[Lr] Data última revisão:
180117
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE


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[PMID]:28466386
[Au] Autor:Wang Z; Guo Y; Han W
[Ad] Endereço:Molecular & Immunological Department, Bio-therapeutic Department, Chinese PLA General Hospital, Beijing, 100853, China.
[Ti] Título:Current status and perspectives of chimeric antigen receptor modified T cells for cancer treatment.
[So] Source:Protein Cell;8(12):896-925, 2017 Dec.
[Is] ISSN:1674-8018
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Chimeric antigen receptor (CAR) is a recombinant immunoreceptor combining an antibody-derived targeting fragment with signaling domains capable of activating cells, which endows T cells with the ability to recognize tumor-associated surface antigens independent of the expression of major histocompatibility complex (MHC) molecules. Recent early-phase clinical trials of CAR-modified T (CAR-T) cells for relapsed or refractory B cell malignancies have demonstrated promising results (that is, anti-CD19 CAR-T in B cell acute lymphoblastic leukemia (B-ALL)). Given this success, broadening the clinical experience of CAR-T cell therapy beyond hematological malignancies has been actively investigated. Here we discuss the basic design of CAR and review the clinical results from the studies of CAR-T cells in B cell leukemia and lymphoma, and several solid tumors. We additionally discuss the major challenges in the further development and strategies for increasing anti-tumor activity and safety, as well as for successful commercial translation.
[Mh] Termos MeSH primário: Imunidade Celular
Imunoterapia
Leucemia-Linfoma Linfoblástico de Células Precursoras B
Receptores de Antígenos de Linfócitos T/imunologia
Proteínas Recombinantes de Fusão/imunologia
Linfócitos T
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
Linfócitos T/imunologia
Linfócitos T/transplante
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Receptors, Antigen, T-Cell); 0 (Recombinant Fusion Proteins)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1007/s13238-017-0400-z


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[PMID]:28973700
[Au] Autor:Alsadi A; Lin D; Alnajar H; Brickman A; Martyn C; Gattuso P
[Ad] Endereço:From the Department of Pathology, Rush University Medical Center, Chicago, Illinois.
[Ti] Título:Hematologic Malignancies Discovered on Investigation of Breast Abnormalities.
[So] Source:South Med J;110(10):614-620, 2017 Oct.
[Is] ISSN:1541-8243
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Hematological malignancies of the breast share a presentation similar to primary breast carcinomas but differ substantially in therapeutic approach and clinical outcomes. In this study, we investigate the frequency of hematological malignancies, their relative primary and secondary occurrences, and further characterize the distinct histopathologies of these malignancies with a special focus on lymphomas. To our knowledge this is one of the largest and most comprehensive studies of breast hematologic malignancies. METHODS: We conducted a retrospective review of our institution's pathology database for hematologic neoplasms diagnosed in breast tissue during a period of 22 years (1992-2014). Clinical characteristics, patient history, histologic subtype, and patient outcomes were analyzed. RESULTS: We identified 52 cases; 46 lymphomas, 4 plasmacytomas, and 2 myeloid sarcomas. The lymphoma cases were 15 diffuse large B-cell lymphomas (DLBCLs), 14 follicular lymphomas (FLs), 8 marginal zone lymphomas (MZLs), 2 anaplastic large T-cell lymphomas, 2 peripheral T-cell lymphomas-not otherwise specified, 1 each of small lymphocytic lymphoma, Burkitt lymphoma, mantle cell lymphoma, B-cell lymphoblastic lymphoma, and T-cell lymphoblastic lymphoma. In total, 30 cases were primary and 22 cases were secondary to the breast. Primary lymphomas accounted for 60% of lymphomas. Most FLs and almost all MZLs were primary. CONCLUSIONS: Primary hematological malignancies of the breast are more common than secondary: 58 % versus 42%. This finding is more evident in lymphomas: 63% versus 37%. The most common hematological malignancy in our study was DLBCL, followed by FL and MZL. Most FLs and almost all MZLs were primary. At the same time, the percentage of primary DLBCLs in our study is lower than the percentage reported in previous studies. We suggest that this could be the result of transformation from low-grade lymphomas. Although rare, hematological malignancies of the breast warrant a higher level of clinical suspicion as they present similarly to breast carcinomas but require a substantially different therapeutic approach.
[Mh] Termos MeSH primário: Neoplasias da Mama/diagnóstico
Carcinoma/diagnóstico
Neoplasias Hematológicas/diagnóstico
Linfoma/diagnóstico
Plasmocitoma/diagnóstico
Sarcoma Mieloide/diagnóstico
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Neoplasias da Mama/patologia
Neoplasias da Mama/secundário
Linfoma de Burkitt/diagnóstico
Linfoma de Burkitt/patologia
Diagnóstico Diferencial
Feminino
Neoplasias Hematológicas/patologia
Seres Humanos
Leucemia Linfocítica Crônica de Células B/diagnóstico
Leucemia Linfocítica Crônica de Células B/patologia
Linfoma/patologia
Linfoma de Zona Marginal Tipo Células B/diagnóstico
Linfoma de Zona Marginal Tipo Células B/patologia
Linfoma Folicular/diagnóstico
Linfoma Folicular/patologia
Linfoma Difuso de Grandes Células B/diagnóstico
Linfoma Difuso de Grandes Células B/patologia
Linfoma Anaplásico de Células Grandes/diagnóstico
Linfoma Anaplásico de Células Grandes/patologia
Linfoma de Célula do Manto/diagnóstico
Linfoma de Célula do Manto/patologia
Linfoma de Células T/diagnóstico
Linfoma de Células T/patologia
Meia-Idade
Plasmocitoma/patologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico
Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia
Estudos Retrospectivos
Sarcoma Mieloide/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.14423/SMJ.0000000000000710


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[PMID]:28892661
[Au] Autor:Mohammadi SM; Mohammadnejad D; Hosseinpour Feizi AA; Movassaghpour AA; Montazersaheb S; Nozad Charoudeh H
[Ad] Endereço:Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
[Ti] Título:Inhibition of c-REL using siRNA increased apoptosis and decreased proliferation in pre-B ALL blasts: Therapeutic implications.
[So] Source:Leuk Res;61:53-61, 2017 Oct.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The c-Rel transcription factor is a unique member of the NF-kB family that has a role in apoptosis, proliferation and cell survival. Overexpression of c-Rel is detected in many human B cell tumors, including B-cell leukemia and several cancers. The study aimed to investigate the effects of c-Rel siRNA on the proliferation and apoptosis of relapsed pre-B acute leukemia cells. The c-Rel siRNA was transfected into Leukemia cells using an Amaxa cell line Nucleofector kit L (Lonza). Quantitative real-time RT-PCR (qRT-PCR) and western blot were done to measure the expression levels of mRNA and protein, respectively. The flow cytometry was used to analyze the effect of c-Rel siRNA on the apoptosis and proliferation of Leukemia cells. Observed c-Rel expression in the 5 pre-B Acute lymphoblastic leukemia (ALL) patients were higher than the normal cells. The c-Rel siRNA transfection significantly blocked the expression of c-Rel mRNA in a time-dependent manner, leading to a strong growth inhibition and enhanced apoptosis (P<0.05). Our results demonstrated that c-Rel plays a fundamental role in the survival. Therefore, c-Rel can be considered as an attractive target for gene therapy in ALL patients. Also siRNA-mediated silencing of this gene may be a novel strategy in ALL treatment.
[Mh] Termos MeSH primário: Apoptose/fisiologia
Técnicas de Silenciamento de Genes/métodos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
Proteínas Proto-Oncogênicas c-rel/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adolescente
Western Blotting
Proliferação Celular/genética
Células Cultivadas
Criança
Pré-Escolar
Feminino
Citometria de Fluxo
Terapia Genética/métodos
Seres Humanos
Masculino
Proteínas Proto-Oncogênicas c-rel/genética
RNA Interferente Pequeno
Reação em Cadeia da Polimerase em Tempo Real
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins c-rel); 0 (RNA, Small Interfering)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE


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[PMID]:28869817
[Au] Autor:Younesian S; Shahkarami S; Ghaffari P; Alizadeh S; Mehrasa R; Ghavamzadeh A; Ghaffari SH
[Ad] Endereço:Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Hematology, School of Allied Medical Sciences, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:DNA hypermethylation of tumor suppressor genes RASSF6 and RASSF10 as independent prognostic factors in adult acute lymphoblastic leukemia.
[So] Source:Leuk Res;61:33-38, 2017 Oct.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The Hypermethylation of Ras association domain family (RASSF) often plays a key role in malignant progression of solid tumors; however, their impact on the prognosis and survival of adult ALL patients remain elusive. METHODS: The frequency of the promoter methylation pattern of RASSF6 and RASSF10 were analyzed in the peripheral blood (PB) samples taken at the time of diagnosis of 45 ALL patients. The methylation-specific PCR (MSP) assay was used to detect the DNA methylation patterns. RESULTS: RASSF6 was frequently hypermethylated in patients diagnosed with pre-B-ALL (90.9%) and B-ALL (87.5%), followed by T-ALL (66.7%); whereas, RASSF10 methylation was more confined to T-ALL (80%) as compared to B-ALL (25%) and pre-B ALL (9.1%) patients. Moreover, hypermethylation of RASSF6 was significantly associated with a poor prognosis and shorter overall survival (OS) in patients with pre-B-ALL (log-rank test; P=0.041). CONCLUSION: RASSF6 and RASSF10 were frequently hypermethylated in the samples at the time of diagnosis of adult ALL patients. Our study represents the first report of methylation of RASSF6 at a high frequency in patients with pre-B ALL. Furthermore, hypermethylation of RASSF6 was significantly associated with inferior overall survival in pre-B ALL patients. It may suggest that the frequent epigenetic inactivation of RASSF6 plays an important role in the pathogenesis and progression of pre-B-ALL.
[Mh] Termos MeSH primário: Metilação de DNA/genética
Proteínas Monoméricas de Ligação ao GTP/genética
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Feminino
Seres Humanos
Estimativa de Kaplan-Meier
Masculino
Meia-Idade
Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade
Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade
Prognóstico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RASSF10 protein, human); 0 (RASSF6 protein, human); 0 (Tumor Suppressor Proteins); EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170905
[St] Status:MEDLINE


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[PMID]:28825327
[Au] Autor:Wilke AC; Gökbuget N
[Ad] Endereço:a University Hospital , Department of Medicine II , Frankfurt , Germany.
[Ti] Título:Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab.
[So] Source:Expert Opin Drug Saf;16(10):1191-1202, 2017 Oct.
[Is] ISSN:1744-764X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Blinatumomab is a T-cell engager antibody construct with dual specificity for CD19 and CD3, inducing serial lysis of CD19 positive B cells by redirecting cytotoxic T cells. It has been approved for the indication of Ph chromosome negative relapsed or refractory B-acute lymphoblastic leukemia (ALL), but has also been tested in ALL with minimal residual disease, relapsed Ph/BCR-ABL positive ALL, relapsed ALL in pediatric patients and relapsed or refractory non-Hodgkin's lymphoma (NHL). Adverse events have been mainly related to infection and hematological toxicities, as well as cytokine release syndrome and neurotoxicity. Areas covered: The review will discuss mechanisms of action, published literature on efficacy in ALL and NHL, specific aspects of administration, frequent adverse events and practical management. Expert opinion: Blinatumomab represents an effective new treatment for highly resistant relapsed/refractory B-precursor ALL. Practical handling bears challenges due to application as four week continous infusion and specific adverse effects which can be well handled by experienced centers. Most promising outcomes are reported for patients with resistant disease but lower tumor load such as MRD positive ALL patients. Future studies will focus on the use of blinatumomab during first-line therapy and the role of stem cell transplantation after blinatumomab treatment.
[Mh] Termos MeSH primário: Anticorpos Biespecíficos/administração & dosagem
Antineoplásicos/administração & dosagem
Linfoma não Hodgkin/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
[Mh] Termos MeSH secundário: Anticorpos Biespecíficos/efeitos adversos
Antígenos CD19/imunologia
Antineoplásicos/efeitos adversos
Seres Humanos
Linfoma não Hodgkin/imunologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/imunologia
Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Bispecific); 0 (Antigens, CD19); 0 (Antineoplastic Agents); 4FR53SIF3A (blinatumomab)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170822
[St] Status:MEDLINE
[do] DOI:10.1080/14740338.2017.1338270


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[PMID]:28818808
[Au] Autor:Yao C; Zhang G; Walker A; Zhao KY; Li Y; Lyu L; Tang Y; Ru P; Jones D; Zhao W
[Ad] Endereço:Department of Hematology, The Third Xiang-ya Hospital of Central South University, Changsha, China.
[Ti] Título:Potent induction of apoptosis by givinostat in BCR-ABL1-positive and BCR-ABL1-negative precursor B-cell acute lymphoblastic leukemia cell lines.
[So] Source:Leuk Res;60:129-134, 2017 Sep.
[Is] ISSN:1873-5835
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We have previously shown that givinostat can induce potent apoptosis in the BCR-ABL1-positive, TP53-wild type B-cell acute lymphoblastic leukemia (B-ALL) cell line SUP-B15. We extend our studies here to two additional B-ALL cell lines, BCR-ABL1-negative CCRF-SB and p210 BCR-ABL1-positive NAML1. Givinostat induced significant cell growth inhibition in both cell lines, with an IC50 of 0.65±0.052µM and 0.25±0.028µM in CCRF-SB and NAML1, respectively. The key signal protein of the BCR-ABL1, Crk-L1, was significantly reduced by givinostat treatment in NAML1. As in SUP-B15, givinostat induced apoptosis in both cell lines but showed different levels of cleavage of the procaspase proteins Casp-3, Casp-7 and PARP. Levels of cell cycle-DNA repair regulator p21, CHK1 and FANCD2 levels were markedly affected by givinostat treatment. These data further enrich our understanding of the mechanisms of the antineoplastic effects of givinostat in B-ALL and provide a preclinical rationale for the inclusion of givinostat or similar agent in leukemia therapy.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Carbamatos/farmacologia
Proteínas de Fusão bcr-abl
Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico
[Mh] Termos MeSH secundário: Carbamatos/uso terapêutico
Caspases/efeitos dos fármacos
Caspases/metabolismo
Ciclo Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Inibidores de Histona Desacetilases
Seres Humanos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carbamates); 0 (Histone Deacetylase Inhibitors); 5P60F84FBH (givinostat); EC 2.7.10.2 (Fusion Proteins, bcr-abl); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170819
[St] Status:MEDLINE


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[PMID]:28790105
[Au] Autor:Lafage-Pochitaloff M; Baranger L; Hunault M; Cuccuini W; Lefebvre C; Bidet A; Tigaud I; Eclache V; Delabesse E; Bilhou-Nabéra C; Terré C; Chapiro E; Gachard N; Mozziconacci MJ; Ameye G; Porter S; Grardel N; Béné MC; Chalandon Y; Graux C; Huguet F; Lhéritier V; Ifrah N; Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
[Ad] Endereço:Department of Genetics, University Hospital, Assistance Publique-Hôpitaux de Marseille, INSERM 1104, Aix-Marseille University, Marseille, France.
[Ti] Título:Impact of cytogenetic abnormalities in adults with Ph-negative B-cell precursor acute lymphoblastic leukemia.
[So] Source:Blood;130(16):1832-1844, 2017 Oct 19.
[Is] ISSN:1528-0020
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)-2003/2005 trials. Combined data from karyotype, DNA index, fluorescence in situ hybridization, and polymerase chain reaction screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in 10 exclusive primary cytogenetic subgroups and in secondary subgroups, including complex and monosomal karyotypes. Prognostic analyses focused on cumulative incidence of failure (including primary refractoriness and relapse), event-free survival, and overall survival. Only 2 subgroups, namely t(4;11)/ and 14q32/ translocations, displayed a significantly worse outcome in this context, still observed after adjustment for age and after censoring patients who received allogeneic stem cell transplantation (SCT) in first remission at SCT time. A worse outcome was also observed in patients with low hypodiploidy/near triploidy, but this was likely related to their higher age and worse tolerance to therapy. The other cytogenetic abnormalities, including complex and monosomal karyotypes, had no prognostic value in these intensive protocols designed for adult patients up to the age of 60 years.
[Mh] Termos MeSH primário: Aberrações Cromossômicas
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico
Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Aberrações Cromossômicas/estatística & dados numéricos
Ensaios Clínicos como Assunto/estatística & dados numéricos
Análise Citogenética
Feminino
Seres Humanos
Cariotipagem
Masculino
Meia-Idade
Estudos Multicêntricos como Assunto/estatística & dados numéricos
Cromossomo Filadélfia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia
Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia
Valor Preditivo dos Testes
Prognóstico
Estudos Retrospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170810
[St] Status:MEDLINE
[do] DOI:10.1182/blood-2017-05-783852



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