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1.
Br J Nurs ; 28(15): 985-992, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31393775

RESUMO

Leukaemia is the most common cancer in children. The presenting manifestations can be wide-ranging, from a relatively well child to life-threatening complications. Symptoms can be manifested in any of the bodily systems. Undertaking a thorough clinical assessment of the child, in addition to recognising and addressing parental concerns, is vital. Furthermore, recognising that children can commonly present with musculoskeletal or abdominal symptoms increases the diagnostic yield, thereby preventing missed or late diagnoses. Childhood cancer has a huge impact on the child and their family, both at diagnosis and in the long term; providing advice and signposting families to appropriate support groups is an important aspect of their management. Nurses play a vital role in managing children with cancers, starting from raising suspicion and identifying the child with leukaemia, ensuring that high-quality care is delivered throughout their treatment, managing complications, and providing support and information to children and their families. An illustrative case study is included to highlight some of the challenges that health professionals may encounter in their clinical practice.


Assuntos
Leucemia/enfermagem , Diagnóstico de Enfermagem , Enfermagem Pediátrica , Criança , Diagnóstico Diferencial , Humanos , Leucemia/classificação , Leucemia/epidemiologia , Fatores de Risco
2.
J Clin Pathol ; 72(11): 755-761, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31256009

RESUMO

AIMS: Morphological differentiation among different blast cell lineages is a difficult task and there is a lack of automated analysers able to recognise these abnormal cells. This study aims to develop a machine learning approach to predict the diagnosis of acute leukaemia using peripheral blood (PB) images. METHODS: A set of 442 smears was analysed from 206 patients. It was split into a training set with 75% of these smears and a testing set with the remaining 25%. Colour clustering and mathematical morphology were used to segment cell images, which allowed the extraction of 2,867 geometric, colour and texture features. Several classification techniques were studied to obtain the most accurate classification method. Afterwards, the classifier was assessed with the images of the testing set. The final strategy was to predict the patient's diagnosis using the PB smear, and the final assessment was done with the cell images of the smears of the testing set. RESULTS: The highest classification accuracy was achieved with the selection of 700 features with linear discriminant analysis. The overall classification accuracy for the six groups of cell types was 85.8%, while the overall classification accuracy for individual smears was 94% as compared with the true confirmed diagnosis. CONCLUSIONS: The proposed method achieves a high diagnostic precision in the recognition of different types of blast cells among other mononuclear cells circulating in blood. It is the first encouraging step towards the idea of being a diagnostic support tool in the future.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Leucemia/patologia , Leucócitos/patologia , Aprendizado de Máquina , Reconhecimento Automatizado de Padrão/métodos , Coloração e Rotulagem/métodos , Doença Aguda , Coleta de Amostras Sanguíneas , Linhagem da Célula , Diagnóstico Diferencial , Humanos , Leucemia/sangue , Leucemia/classificação , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
3.
Pathobiology ; 86(1): 39-52, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29961056

RESUMO

Hypereosinophilia (HE) is defined as a persistent elevated eosinophil count of ≥1.5 × 109/L. HE can be one of the dominant manifestations of a hematopoietic myeloid neoplasm or secondary/reactive to an underlying medical condition. If a cause of HE and its associated tissue/organ damage is not determined, the condition is considered to be idiopathic hypereosinophilic syndrome (HES). The work-up of HE can be challenging due to a broad range of causes of HE that can be either reactive or neoplastic. In recent years, with the advent of molecular genetic testing and the introduction of targeted therapy in the management of these patients, there is a growing interest in better characterization of these diseases. Using a multimodality approach and following a proper -algorithm, a diagnosis can be made in a large proportion of patients. In idiopathic HES, myeloid neoplasm associated -somatic mutations as evidence of clonality are reported in -20-25% patients; however, the mutation data should be -interpreted cautiously considering the prevalence of clonal hematopoiesis of indeterminate potential (CHIP). Bone marrow morphology has been shown to have important value in the identification of a true myeloid neoplasm in these disorders. A genome-wide study may be needed to understand the "idiopathic" cases that would ultimately lead to better patient care.


Assuntos
Síndrome Hipereosinofílica/diagnóstico , Leucemia/diagnóstico , Transtornos Mieloproliferativos/diagnóstico , Algoritmos , Medula Óssea/patologia , Eosinófilos/patologia , Estudo de Associação Genômica Ampla , Hematopoese , Humanos , Síndrome Hipereosinofílica/classificação , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/patologia , Leucemia/classificação , Leucemia/genética , Leucemia/patologia , Mutação , Transtornos Mieloproliferativos/classificação , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologia
4.
Cancer ; 124(22): 4301-4313, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30291792

RESUMO

Historically, progress in leukemia research has been slow, but it has accelerated recently as a result of understanding the pathophysiology of leukemias and implementing more effective and targeted therapies. This review summarizes the progress across leukemia subsets and projects the potential cure of most leukemias in the next decade.


Assuntos
Leucemia/classificação , Leucemia/terapia , Antineoplásicos/uso terapêutico , Intervalo Livre de Doença , Humanos , Leucemia/genética , Padrão de Cuidado , Transplante de Células-Tronco , Resultado do Tratamento
5.
Cancer ; 124(19): 3856-3867, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30343495

RESUMO

BACKGROUND: The lifetime risk of developing leukemia in the United States is 1.5%. There are challenges in the estimation of population-based survival using registry data because treatments and prognosis vary greatly by subtype. The objective of the current study was to determine leukemia survival estimates in the United States from 1995 to 2009 according to subtype, sex, geographical area, and race. METHODS: Five-year net survival was estimated using data for 370,994 patients from 43 registries in 37 states and in 6 metropolitan areas, covering approximately 81% of the adult (15-99 years) US population. Leukemia was categorized according to principal subtype (chronic lymphocytic leukemia, acute myeloid leukemia, and acute lymphocytic leukemia), and subcategorized in accordance with the HAEMACARE protocol. We analyzed age-standardized 5-year net survival by calendar period (1995-1999, 2000-2004, and 2005-2009), leukemia subtype, sex, race, and US state. RESULTS: The age-standardized 5-year net survival estimates increased from 45.0% for patients diagnosed during 1995-1999 to 49.0% for those diagnosed during 2000-2004 and 52.0% for those diagnosed during 2005-2009. For patients diagnosed during 2005-2009, 5-year survival was 18.2% (95% confidence interval [95% CI], 17.8%-18.6%) for acute myeloid leukemia, 44.0% (95% CI, 43.2%-44.8%) for acute lymphocytic leukemia, and 77.3% (95% CI, 76.9%-77.7%) for chronic lymphocytic leukemia. For nearly all leukemia subtypes, survival declined in successive age groups above 45 to 54 years. Men were found to have slightly lower survival than women; however, this discrepancy was noted to have fallen in successive calendar periods. Net survival was substantially higher in white than black patients in all calendar periods. There were large differences in survival noted between states and metropolitan areas. CONCLUSIONS: Survival from leukemia in US adults improved during 1995-2009. Some geographical differences in survival may be related to access to care. We found disparities in survival by sex and between black and white patients.


Assuntos
Leucemia/classificação , Leucemia/mortalidade , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Leucemia/diagnóstico , Leucemia/epidemiologia , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Sistema de Registros/estatística & dados numéricos , Programa de SEER , Análise de Sobrevida , Estados Unidos/epidemiologia , Adulto Jovem
6.
Blood ; 132(4): 413-422, 2018 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-29769262

RESUMO

Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy, but some patients have a very indolent evolution. This heterogeneous course is related, in part, to the different biological characteristics of conventional MCL (cMCL) and the distinct subgroup of leukemic nonnodal MCL (nnMCL). Robust criteria to distinguish these MCL subtypes and additional biological parameters that influence their evolution are not well defined. We describe a novel molecular assay that reliably distinguishes cMCL and nnMCL using blood samples. We trained a 16-gene assay (L-MCL16 assay) on the NanoString platform using 19 purified leukemic samples. The locked assay was applied to an independent cohort of 70 MCL patients with leukemic presentation. The assay assigned 37% of cases to nnMCL and 56% to cMCL. nnMCL and cMCL differed in nodal presentation, lactate dehydrogenase, immunoglobulin heavy chain gene mutational status, management options, genomic complexity, and CDKN2A/ATM deletions, but the proportion with 17p/TP53 aberrations was similar in both subgroups. Sequential samples showed that assay prediction was stable over time. nnMCL had a better overall survival (OS) than cMCL (3-year OS 92% vs 69%; P = .006) from the time of diagnosis and longer time to first treatment. Genomic complexity and TP53/CDKN2A aberrations predicted for shorter OS in the entire series and cMCL, whereas only genomic complexity was associated with shorter time to first treatment and OS in nnMCL. In conclusion, the newly developed assay robustly recognizes the 2 molecular subtypes of MCL in leukemic samples. Its combination with genetic alterations improves the prognostic evaluation and may provide useful biological information for management decisions.


Assuntos
Biomarcadores Tumorais/genética , Leucemia/genética , Leucemia/patologia , Linfoma de Célula do Manto/genética , Linfoma de Célula do Manto/patologia , Mutação , Estudos de Coortes , Feminino , Perfilação da Expressão Gênica , Genômica , Humanos , Leucemia/classificação , Linfoma de Célula do Manto/classificação , Masculino , Prognóstico , Taxa de Sobrevida
7.
Comput Methods Programs Biomed ; 158: 93-112, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29544792

RESUMO

CONTEXT: Acute leukaemia diagnosis is a field requiring automated solutions, tools and methods and the ability to facilitate early detection and even prediction. Many studies have focused on the automatic detection and classification of acute leukaemia and their subtypes to promote enable highly accurate diagnosis. OBJECTIVE: This study aimed to review and analyse literature related to the detection and classification of acute leukaemia. The factors that were considered to improve understanding on the field's various contextual aspects in published studies and characteristics were motivation, open challenges that confronted researchers and recommendations presented to researchers to enhance this vital research area. METHODS: We systematically searched all articles about the classification and detection of acute leukaemia, as well as their evaluation and benchmarking, in three main databases: ScienceDirect, Web of Science and IEEE Xplore from 2007 to 2017. These indices were considered to be sufficiently extensive to encompass our field of literature. RESULTS: Based on our inclusion and exclusion criteria, 89 articles were selected. Most studies (58/89) focused on the methods or algorithms of acute leukaemia classification, a number of papers (22/89) covered the developed systems for the detection or diagnosis of acute leukaemia and few papers (5/89) presented evaluation and comparative studies. The smallest portion (4/89) of articles comprised reviews and surveys. DISCUSSION: Acute leukaemia diagnosis, which is a field requiring automated solutions, tools and methods, entails the ability to facilitate early detection or even prediction. Many studies have been performed on the automatic detection and classification of acute leukaemia and their subtypes to promote accurate diagnosis. CONCLUSIONS: Research areas on medical-image classification vary, but they are all equally vital. We expect this systematic review to help emphasise current research opportunities and thus extend and create additional research fields.


Assuntos
Leucemia/classificação , Leucemia/diagnóstico , Motivação , Doença Aguda , Algoritmos , Automação , Conjuntos de Dados como Assunto , Detecção Precoce de Câncer , Humanos , Reprodutibilidade dos Testes
8.
Indian Pediatr ; 55(1): 55-62, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29396936

RESUMO

The utility of flow cytometry as a useful diagnostic modality for the assessment of hematopoietic neoplasms has been established beyond doubt. In fact, it is now an integral part of the diagnosis and classification of various diseases like leukemias and lymphomas along with molecular studies and cytogenetics. Prognostication and disease monitoring by flow cytometry is also being recognized increasingly as one of the important fortes. This is evident by the number of articles in the published in literature on the minimal residual disease detection by flow cytometry especially in the last decade or so. To add to this, ever growing list of utilities in hematopoietic malignancies, many non-hematopoietic neoplasms can also be analyzed by flow cytometry. The examples include fluid specimens from serous cavity effusions and samples from solid tissues like lymph nodes, reticulo-endothelial tissue, central nervous system tissue, etc. Flow cytometry technique provides a unique blend of rapidity, high sensitivity and specificity compared to cyto-morphology and conventional immunohistochemical staining. It is also remarkable for simultaneous analysis of more than one marker on the cells. Evaluation of limited samples such as cerebrospinal fluid or fine needle aspiration samples makes Flow cytometry a valuable tool. DNA ploidy analysis and assessment of pediatric non-hematopoietic neoplasms by Flow cytometry has envisaged the utility vista of this technique. This review is aimed at providing an insight into the applications of flow cytometry in pediatric malignancies.


Assuntos
Citometria de Fluxo , Imunofenotipagem , Leucemia , Linfoma , Antígenos CD , Pré-Escolar , Humanos , Leucemia/classificação , Leucemia/diagnóstico , Linfoma/classificação , Linfoma/diagnóstico
9.
J Clin Lab Anal ; 32(5): e22392, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29356090

RESUMO

BACKGROUND: Automated cell counters have become more and more sophisticated with passing years. The numerical and graphic data both provide useful clues for suspecting a diagnosis especially when the workload is very high. AIM: We present our experience of useful information provided by graphic displays of an automated cell counter in hematological malignancies in a cancer hospital where a large number of complete blood count (CBC) requests are received either before or during chemotherapy. This study was conducted to assess the usefulness of hematology cell counter, viz. WBC-Diff (WBC differential), WBC/BASO (WBC basophil) and IMI (immature myeloid information) channel scatter plots, and the flaggings generated in various hematological malignancies. MATERIAL & METHODS: The graphic displays have been compiled over a period of 1 year (October 2015-September 2016) from blood samples of various solid and hematological malignancies (approximately 400 per day) received for routine CBC in the laboratory. Approximately 50 000 scattergrams have been analyzed during the study period. The findings were confirmed by peripheral blood smear examination. RESULTS: The scattergram analysis on XE-2100 is very sensitive as well as specific for diagnosing acute leukemia, viz. acute myeloid leukemia, acute lymphoblastic leukemia; chronic myeloproliferative disorders, viz. chronic myeloid leukemia; and chronic lymphoproliferative disorder especially chronic lymphocytic leukemia. CONCLUSION: It is suggested that the laboratories using the hematology analyzers be aware of graphic display patterns in addition to flaggings generated which provide additional information and give clue toward the diagnosis even before peripheral smear examination.


Assuntos
Automação Laboratorial/métodos , Neoplasias Hematológicas/diagnóstico , Testes Hematológicos , Transtornos Mieloproliferativos/diagnóstico , Contagem de Células , Neoplasias Hematológicas/classificação , Humanos , Leucemia/classificação , Leucemia/diagnóstico , Contagem de Leucócitos
10.
Cancer Lett ; 418: 10-19, 2018 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-29331412

RESUMO

The peroxisome proliferator-activated receptor (PPAR) γ, a subtype of PPARs, is a member of the nuclear receptor family. PPARγ and its ligands contribute to various types of diseases including cancer. Given that currently developed therapies against leukemia are not very effective or safe, PPARγ ligands have been shown to be a new class of compounds with the potential to treat hematologic malignancies, particularly leukemia. The capability of PPARγ ligands to induce apoptosis, inhibit proliferation, and promote differentiation of leukemia cells suggests it has significant potential as a drug against leukemia. However, the specific mechanisms and molecules involved are not well-understood, although a number of PPARγ ligands with anti-leukemic effects have been identified. This may explain why PPARγ ligands have not been widely evaluated in clinical trials. To fill the gaps in the lack of understanding of specific anti-leukemic processes of PPARγ ligands and further adapt these molecules as anti-leukemic agents, this review describes previous studies of the anti-leukemic effects of PPARγ ligands.


Assuntos
Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Leucemia/tratamento farmacológico , PPAR gama/agonistas , PPAR gama/antagonistas & inibidores , Tiazolidinedionas/uso terapêutico , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Humanos , Leucemia/classificação , Leucemia/metabolismo , Ligantes , Modelos Biológicos , PPAR gama/metabolismo
11.
Sci Rep ; 8(1): 548, 2018 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-29323237

RESUMO

Leukemia is a malignant progressive disease and has four major subtypes. Different racial groups differ significantly in multiple aspects. Our goal is to systematically and comprehensively quantify racial differences in leukemia. The SEER database is analyzed, and comprehensive descriptive analysis is provided for the four major subtypes, namely ALL (acute lymphoblastic leukemia), CLL (chronic lymphoblastic leukemia), AML (acute myeloid leukemia), and CML (chronic myeloid leukemia), and for two age groups (≤14 and >14) separately. The racial groups studied include NHW (non-Hispanic White), HW (Hispanic White), BL (Black), and API (Asian and Pacific Islander). Univariate and multivariate analyses are conducted to quantify racial differences in patients' characteristics, incidence, and survival. For patients' characteristics, significant racial differences are observed in gender, age at diagnosis, diagnosis era, using radiation for treatment, registry, cancer history, and histology type. For incidence, significant racial differences are observed, and the patterns vary across subtypes, gender, and age groups. For most of the subtypes and gender and age groups, Blacks have the worst five-year survival, and significant racial differences exist. This study provides a comprehensive epidemiologic description of racial differences for the four major leukemia subtypes in the U.S.


Assuntos
Grupos de Populações Continentais/estatística & dados numéricos , Leucemia/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Leucemia/classificação , Leucemia/etnologia , Masculino , Estados Unidos
12.
Vet Pathol ; 55(1): 159-172, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28812528

RESUMO

Leukemia is broadly divided into acute and chronic lymphocytic and myeloid types based on the proportion of blasts, morphology of cells, and expression of specific antigens on neoplastic cells. Classifying leukemia in horses can be challenging if blasts predominate and since few antibodies to identify cell types are available. The objective of this study was to describe in detail the clinical and pathologic features of acute leukemia in horses. Twelve horses ranging from 0.2 to 25.9 years of age were diagnosed with acute leukemia. Six cases were classified as acute lymphocytic leukemia (ALL) based on predominance of blasts, lack of granulocytic or monocytic differentiation, and detection of CD3, CD20, and/or CD79a antigens by immunohistochemistry. Six other cases were classified as acute myeloid leukemia (AML) with myelomonocytic ( n = 4), basophilic ( n = 1), and eosinophilic ( n = 1) differentiation based on > 20% bone marrow blasts and partial leukocytic differentiation. Reactivity with antibodies to Iba-1/AIF-1, CD172a, and CD163 was determined for all cases of AML. Eleven horses had thrombocytopenia, 10 had neutropenia, 8 had anemia, all had blasts on blood films, and none had leukocytosis. Ten horses had increased serum acute phase proteins. Bone marrow cellularity ranged from 30% to 100%, and the proportion of blasts ranged from 80% to 100% and 30% to 60% in ALL and AML, respectively. Horses were severely ill at diagnosis and euthanized within days or weeks. Unique features of acute leukemia in horses compared to other species were variable lymphocyte antigen expression (ALL) and frequent inflammation (ALL and AML).


Assuntos
Doenças dos Cavalos/patologia , Leucemia/patologia , Animais , Progressão da Doença , Doenças dos Cavalos/classificação , Cavalos , Leucemia/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombocitopenia/patologia
13.
Eur Rev Med Pharmacol Sci ; 21(4 Suppl): 31-36, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29165768

RESUMO

Leukemia is defined as an aberrant hyper-proliferation of immature blood cells that do not form solid tumor masses (i.e., liquid cancer). Usually, leukemia could be either of the myeloid or lymphoid lineages, and is classified as acute or chronic in nature. Chronic leukemias tend to have more mature cells and are rare in pediatric patients. Acute leukemias, on the other hand, are typically less mature and commonly occur in patients of all ages and are potentially rapidly fatal if not readily treated. The acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Similar to AML, and in some cases, on the same disease spectrum, are the myelodysplastic syndromes (MDS). The present review is focused on the recent perspectives of pediatric leukemia.


Assuntos
Leucemia/classificação , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Doença Aguda , Doença Crônica , Humanos , Leucemia/tratamento farmacológico , Leucemia/genética , Leucemia/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Fatores de Risco
14.
Bioinformatics ; 33(18): 2897-2905, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28431087

RESUMO

Motivation: This work addresses two common issues in building classification models for biological or medical studies: learning a sparse model, where only a subset of a large number of possible predictors is used, and training in the presence of missing data. This work focuses on supervised generative binary classification models, specifically linear discriminant analysis (LDA). The parameters are determined using an expectation maximization algorithm to both address missing data and introduce priors to promote sparsity. The proposed algorithm, expectation-maximization sparse discriminant analysis (EM-SDA), produces a sparse LDA model for datasets with and without missing data. Results: EM-SDA is tested via simulations and case studies. In the simulations, EM-SDA is compared with nearest shrunken centroids (NSCs) and sparse discriminant analysis (SDA) with k-nearest neighbors for imputation for varying mechanism and amount of missing data. In three case studies using published biomedical data, the results are compared with NSC and SDA models with four different types of imputation, all of which are common approaches in the field. EM-SDA is more accurate and sparse than competing methods both with and without missing data in most of the experiments. Furthermore, the EM-SDA results are mostly consistent between the missing and full cases. Biological relevance of the resulting models, as quantified via a literature search, is also presented. Availability and implementation: A Matlab implementation published under GNU GPL v.3 license is available at http://web.mit.edu/braatzgroup/links.html . Contact: braatz@mit.edu. Supplementary information: Supplementary data are available at Bioinformatics online.


Assuntos
Biologia Computacional/métodos , Modelos Biológicos , Software , Infecções Bacterianas/classificação , Infecções Bacterianas/genética , Classificação , Genes , Humanos , Leucemia/classificação , Leucemia/genética , Aprendizado de Máquina
15.
Artigo em Inglês | MEDLINE | ID: mdl-28242784

RESUMO

Recent studies have shown the importance of chromatin-modifying complexes in the maintenance of developmental gene expression and human disease. The mixed lineage leukemia gene (MLL1) encodes a chromatin-modifying protein and was discovered as a result of the cloning of translocations involved in human leukemias. MLL1 is a histone lysine 4 (H3K4) methyltransferase that supports transcription of genes that are important for normal development including homeotic (Hox) genes. MLL1 rearrangements result in expression of fusion proteins without H3K4 methylation activity but may gain the ability to recruit other chromatin-associated complexes such as the H3K79 methyltransferase DOT1L and the super elongation complex. Therefore, chromosomal translocations involving MLL1 appear to directly perturb the regulation of multiple chromatin-associated complexes to allow inappropriate expression of developmentally regulated genes and thus drive leukemia development.


Assuntos
Cromatina/metabolismo , Histona-Lisina N-Metiltransferase/genética , Leucemia/genética , Proteína de Leucina Linfoide-Mieloide/genética , Animais , Expressão Gênica , Humanos , Leucemia/classificação , Leucemia/patologia , Camundongos
16.
Oncotarget ; 8(3): 4387-4398, 2017 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-27966457

RESUMO

The major objective of this study was to examine the association between Methylenetetrahydrofolate Reductase (MTHFR) polymorphisms and the risk of various types of leukemias across the lifespans of children and adults by using the meta-predictive techniques. The secondary objective was to examine the interactions among epigenetic risk factors (including air pollution), MTHFR polymorphisms, and the risks of developing leukemia. We completed a comprehensive search of 6 databases to find 54 studies (10,033 leukemia cases and 15,835 controls) for MTHFR 677, and 43 studies (8,868 cases and 14,301 controls) for MTHFR 1298, published from 1999 to 2014. The results revealed that, in European populations; childhood populations; children from Europe, East Asia, and America; and children with acute lymphocytic leukemia (ALL), MTHFR 677 polymorphisms (both TT and CT types together and individually) are protective, while CC wildtype was leukemogenic. In addition, MTHFR 1298 polymorphisms were protective against ALL and acute myeloid leukemia in European children, and in chronic myeloid leukemia in all adults worldwide and American adults. Air pollution played a role in the increased polymorphisms of MTHFR 677 genotypes in childhood leukemia.


Assuntos
Poluição do Ar/efeitos adversos , Leucemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Polimorfismo Genético , Adulto , África , Fatores Etários , Ásia , Criança , Europa (Continente) , Feminino , Interação Gene-Ambiente , Predisposição Genética para Doença , Genótipo , Humanos , Leucemia/classificação , Masculino , Estados Unidos
18.
Pathologe ; 37(5): 441-8, 2016 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-27491549

RESUMO

The mediastinum is among the most frequent anatomic region in which germ cell tumors (GCT) arise, second only to the gonads. Mediastinal GCT (mGCT) account for 16 % of all mediastinal neoplasms. Although the morphology and (according to all available data) the molecular genetics of mediastinal and gonadal GCT are identical, a number of unique aspects exist. There is a highly relevant bi-modal age distribution. In pre-pubertal children of both sexes, mGCT consist exclusively of teratomas and yolk sac tumors. The prognosis is generally favorable with modern treatment. In post-pubertal adults, virtually all patients with malignant mGCT are males; the prognosis is more guarded and depends (among other factors) on the histological GCT components and is similar to GCT in other organs. So-called somatic type malignancies (i. e. clonally related, non-germ cell neoplasias arising in a GCT) are much more frequent in mGCT than in other organs, and the association between mediastinal yolk sac tumors and hematological malignancies, such as myelodysplasias and leukemias, is unique to mediastinal tumors. The prognosis of GCT with somatic type malignancies is generally dismal.


Assuntos
Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Adulto , Fatores Etários , Criança , Diagnóstico Diferencial , Tumor do Seio Endodérmico/classificação , Tumor do Seio Endodérmico/diagnóstico , Tumor do Seio Endodérmico/patologia , Feminino , Humanos , Imuno-Histoquímica , Leucemia/classificação , Leucemia/diagnóstico , Leucemia/patologia , Masculino , Neoplasias do Mediastino/classificação , Síndromes Mielodisplásicas/classificação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Neoplasias Embrionárias de Células Germinativas/classificação , Prognóstico , Fatores Sexuais , Teratoma/diagnóstico , Teratoma/patologia
19.
Ann Oncol ; 27(4): 725-31, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26812903

RESUMO

BACKGROUND: Current cancer mortality statistics are important for public health decision-making and resource allocation. Age-standardized rates and numbers of deaths are predicted for 2016 in the European Union (EU). PATIENTS AND METHODS: Population and death certification data for stomach, colorectum, pancreas, lung, breast, uterus, prostate, leukaemias and total cancers were obtained from the World Health Organization database and Eurostat. Figures were derived for the EU, France, Germany, Italy, Poland, Spain and the UK. Projected numbers of deaths by age group were obtained for 2016 by linear regression on estimated numbers of deaths over the most recent time period identified by a joinpoint regression model. RESULTS: Projected total cancer mortality trends for 2016 in the EU are favourable in both sexes with rates of 133.5/100 000 men and 85.2/100 000 women (8% and 3% falls since 2011) corresponding to 753 600 and 605 900 deaths in men and women for a total number of 1 359 500 projected cancer deaths (+3% compared with 2011, due to population ageing). In men, lung, colorectal and prostate cancer have fallen 11%, 5% and 8%, respectively, since 2011. Breast and colorectal cancer trends in women are favourable (8% and 7% falls, respectively), but lung and pancreatic cancer rates have risen 5% and 4% since 2011 reaching rates of 14.4 and 5.6/100 000 women. Leukaemias show favourable projected mortality for both sexes and all age groups, with stronger falls in the younger age groups. All ages rates are 4.0/100 000 men and 2.5/100 000 women, with falls of 14% and 12% respectively. CONCLUSION: The 2016 predictions for EU cancer mortality confirm the favourable trends in rates particularly for men. Lung cancer is likely to be the leading site for female cancer rates. Continuing falls in mortality, larger in children and young adults, are predicted in leukaemias, essentially due to advancements in management and therapy, and their subsequent adoption across Europe.


Assuntos
Previsões , Leucemia/mortalidade , Prognóstico , Adulto , Fatores Etários , Idoso , Criança , Europa (Continente)/epidemiologia , Feminino , Humanos , Leucemia/classificação , Leucemia/patologia , Masculino , Pessoa de Meia-Idade
20.
Ann Lab Med ; 36(2): 85-100, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26709255

RESUMO

Chromosomal translocations of the human mixed-lineage leukemia (MLL) gene have been analyzed for more than 20 yr at the molecular level. So far, we have collected about 80 direct MLL fusions (MLL-X alleles) and about 120 reciprocal MLL fusions (X-MLL alleles). The reason for the higher amount of reciprocal MLL fusions is that the excess is caused by 3-way translocations with known direct fusion partners. This review is aiming to propose a solution for an obvious problem, namely why so many and completely different MLL fusion alleles are always leading to the same leukemia phenotypes (ALL, AML, or MLL). This review is aiming to explain the molecular consequences of MLL translocations, and secondly, the contribution of the different fusion partners. A new hypothesis will be posed that can be used for future research, aiming to find new avenues for the treatment of this particular leukemia entity.


Assuntos
Leucemia/genética , Alelos , Cromossomos Humanos X , Epigênese Genética , Humanos , Leucemia/classificação , Leucemia/patologia , Proteína de Leucina Linfoide-Mieloide/química , Proteína de Leucina Linfoide-Mieloide/genética , Estrutura Terciária de Proteína , Translocação Genética
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