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1.
Article in Portuguese | ColecionaSUS, LILACS, ColecionaSUS, CONASS, SES-GO | ID: biblio-1359838

ABSTRACT

Introdução: A L-asparaginase tem sido estudada como alternativa no tratamento da Leucemia Linfoblástica Aguda (LLA) uma vez que possui a capacidade de induzir apoptose em células leucêmicas sem causar danos às células normais. Estudos mostraram benefícios no tratamento da LLA, porém com o risco de desenvolver efeitos adversos. Objetivo: Este trabalho visa apresentar e explicar o histórico da L-asparaginase, desafios enfrentados pelo Brasil, mecanismos de ação que envolvem as formas da enzima e efeitos adversos de sua utilização. Métodos: Foram incluídos neste trabalho 54 artigos na língua portuguesa e inglesa consultados em bancos de artigos como PubMed e SciELO, entre o período de 1953 até 2021. Resultados: A L-asparaginase é uma enzima que converte asparagina em aspartato e amônia, isolada a partir de colônias de Escherichia coli e de Erwinia chrysanthemi, além disso foi polimerizada com polietilenoglicol. O uso de corticosteroides, anti-histamínicos e suplementação vitamínica se mostraram eficientes para amenizar os efeitos adversos. Conclusões: É necessário evitar um desabastecimento de L-Asparaginase no Brasil, principalmente por conta da dificuldade de comercialização e alto custo, mesmo sendo um medicamento presente na lista da Organização Mundial da Saúde, considerado essencial.


Introduction: L-asparaginase has been studied as an alternative in the treatment of Acute Lymphoblastic Leukemia (ALL) since it has the ability to induce apoptosis in leukemic cells without causing damage to normal cells. Studies have shown benefits in the treatment of ALL, but with the risk of developing adverse effects. Objective: This work aims to present and explain the history of L-asparaginase, challenges faced by Brazil, mechanisms of action involving the forms of the enzyme and adverse effects of its use. Methods: 54 articles in Portuguese and English were included in this work, consulted in article banks such as PubMed and SciELO, between the period of 1953 to 2021. Results: L-asparaginase is an enzyme that converts asparagine into aspartate and ammonia, isolated from from Escherichia coli and Erwinia chrysanthemi colonies, it was also polymerized with polyethylene glycol. The use of corticosteroids, antihistamines and vitamin supplementation proved to be efficient in mitigating adverse effects. Conclusions: It is necessary to avoid a shortage of L-Asparaginase in Brazil, mainly due to the difficulty of commercialization and high cost, even though it is a drug present on the World Health Organization list, considered essential.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Asparaginase/antagonists & inhibitors , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/prevention & control , Escherichia coli , Antineoplastic Agents/administration & dosage
2.
Oncol. (Guayaquil) ; 31(2): 141-154, 31 de agosto 2021.
Article in Spanish | LILACS | ID: biblio-1284452

ABSTRACT

Introducción: La leucemia linfoblástica aguda (LLA) es la neoplasia maligna de mayor frecuencia en la infancia; advertir sus alteraciones moleculares y citogenéticas permite establecer el riesgo, el pronóstico asociado y además plantear esquemas terapéuticos apropiados; el objetivo de este estudio es conocer la prevalencia de estas alteraciones en nuestra población. Metodología: Estudio de tipo retrospectivo y transversal, basado en los registros de las alteraciones moleculares y citogenéticas de los pacientes pediátricos diagnosticados con leucemia linfoblástica aguda durante el periodo comprendido entre enero 2014 a diciembre de 2018, en el Hospital del Instituto Oncológico Nacional "Dr. Juan Tanca Marengo". Resultados: Se incluyeron 338 pacientes, de los cuales el principal grupo etario lo constituyo el de 0 a 4 años; el inmunofenotipo más observado fue el B-común. En el 24.56% de los casos se detectó altercaciones estructurales, principalmente por estudios de biología molecular; siendo la más común la translocación t(12;21). Se obtuvieron resultados por citogenética en 167 pacientes, en cuales la principal alteración numérica correspondió a la hiperdiploidía de entre 47 a 51 cromosomas. Conclusión: Los avances en la caracterización molecular y citogenética de la LLA, permiten mejorar la estratificación de su riesgo; y establecer estrategias terapéuticas que permitan una mejoría en la sobrevida.


Introduction: Acute lymphoblastic leukemia (ALL) is the most frequent malignant neoplasm in childhood; Noting its molecular and cytogenetic alterations allows to establish the risk, the associat-ed prognosis and also to propose appropriate therapeutic schemes; The objective of this study is to know the prevalence of these alterations in our population. Methods: Retrospective and cross-sectional study, based on the records of molecular and cytogenetic alterations of pediatric patients diagnosed with acute lymphoblastic leukemia during the period from January 2014 to December 2018, at the National Oncological Institute Hospital "Dr. Juan Tanca Marengo". Results: 338 patients were included, of which the main age group was made up of 0 to 4 years; the most observed immunophenotype was B-common. In 24.56% of the cases, structural alterations were detected, mainly by molecular biology studies; the most common being the t (12; 21) translocation. Cytogenetics results were obtained in 167 patients, in which the main numerical alteration corresponded to hyperdiploidy of between 47 and 51 chromosomes. Conclusions: Advances in the molecular and cytogenetic characterization of ALL make it possible to improve the stratification of its risk; and establish therapeutic strategies that achieve an improvement in survival.


Introdução: A leucemia linfoblástica aguda (LLA) é a neoplasia maligna mais comum na infância; Observar suas alterações moleculares e citogenéticas permite estabelecer o risco, o prognóstico associado e também propor esquemas terapêuticos adequados; O objetivo deste estudo é conhecer a prevalência dessas alterações em nossa população. Metodologia: Estudo retrospectivo e transversal, baseado nos registros de alterações moleculares e citogenéticas de pacientes pediátricos com diagnóstico de leucemia linfoblástica aguda no período de janeiro de 2014 a dezembro de 2018, no Hospital del Instituto Oncológico Nacional "Dr. Juan Tanca Marengo ". Resultados: Foram incluídos 338 pacientes, cuja faixa etária principal era de 0 a 4 anos; o imunofenótipo mais observado foi B-comum. Em 24,56% dos casos, foram detectadas alterações estruturais, principalmente por estudos de biologia molecular; o mais comum é a translocação t (12; 21). Os resultados citogenéticos foram obtidos em 167 pacientes, nos quais a principal alteração numérica correspondeu à hiperdiploidia entre 47 e 51 cromossomos. Conclusão: Os avanços na caracterização molecular e citogenética da LLA permitiram melhorar a estratificação de risco; e estabelecer estratégias terapêuticas que permitam uma melhora na sobrevida.


Subject(s)
Humans , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Leukemia, Biphenotypic, Acute , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Translocation, Genetic , Child , Cytogenetics
3.
Hematol., Transfus. Cell Ther. (Impr.) ; 43(1): 28-34, Jan.-Mar. 2021. tab, graf, ilus
Article in English | LILACS | ID: biblio-1154296

ABSTRACT

ABSTRACT Aberrant expression of long non-coding RNAs (lncRNAs) has been detected in several types of cancer, including acute lymphoblastic leukemia (ALL), but lncRNA mapped on transcribed ultraconserved regions (T-UCRs) are little explored. The T-UCRs uc.112, uc.122, uc.160 and uc.262 were evaluated by quantitative real-time PCR in bone marrow samples from children with T-ALL (n = 32) and common-ALL/pre-B ALL (n = 30). In pediatric ALL, higher expression levels of uc.112 were found in patients with T-ALL, compared to patients with B-ALL. T-cells did not differ significantly from B-cells regarding uc.112 expression in non-tumor precursors from public data. Additionally, among B-ALL patients, uc.112 was also found to be increased in patients with hyperdiploidy, compared to other karyotype results. The uc.122, uc.160, and uc.262 were not associated with biological or clinical features. These findings suggest a potential role of uc.112 in pediatric ALL and emphasize the need for further investigation of T-UCR in pediatric ALL.


Subject(s)
Humans , Female , Diploidy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Bone Marrow , Polymerase Chain Reaction
4.
Journal of Experimental Hematology ; (6): 1471-1477, 2021.
Article in Chinese | WPRIM | ID: wpr-922281

ABSTRACT

OBJECTIVE@#To investigate the optimal time of monitoring minimal residual disease (MRD) for predicting survival and prognosis in children with T-cell acute lymphoblastic leukemia (T-ALL) after treated by CCLG-ALL2008 chemotherapy.@*METHODS@#96 children with T-ALL receiving CCLG-ALL2008 chemotherapy treated in our hospital from January 2015 to January 2020 were retrospectively summarized. The follow-up time was 9.0-65.0 months, with a median of 43.5 months. Kaplan-Meier survival curve was used to detect the overall event-free survival (EFS) and overall survival (OS) of the patients. The clinical data, MRD levels after 15 d, 33 d and 90 d chemotherapy between EFS group and relapse group, as well as OS group and death group were compared by using univariate analysis. Multivariate Logistic regression analysis was used to screen the main risk factors affecting EFS and OS of the patients. The patients were divided into low, moderate and high-risk according to the MRD level after 15 d, 33 d and 90 d, the differences of EFS and OS between each groups were compared again.@*RESULTS@#By the end of follow-up, 50 patients recurred and other 46 patients non-recurred; 40 patients died and 56 patients survived, the EFS was (49.5±6.3)% and OS was (61.5±5.9)%. Univariate analysis showed that the initial WBC count in EFS group (n=46) was significantly lower than that in relapse group (n=50), and MRD levels after 33 d and 90 d were significantly less also (P0.05), however for 90 d, EFS and OS of the patients in high-risk group were significantly lower than those in medium-risk group, and those in medium-risk group were lower than those in low-risk group (P<0.05).@*CONCLUSION@#The MRD level after 90 days CCLG-ALL2008 chemotherapy may be the best time to predict the survival and prognosis in T-ALL children.


Subject(s)
Child , Disease-Free Survival , Humans , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Retrospective Studies , Risk Factors , T-Lymphocytes
5.
Journal of Experimental Hematology ; (6): 1456-1461, 2021.
Article in Chinese | WPRIM | ID: wpr-922279

ABSTRACT

OBJECTIVE@#To investigate the effect of β-arrestin1 on the concentration of reactive oxygen species (ROS) in the mitochondria of acute T-lymphocytic leukemia (T-ALL) cells and its possible mechanisms.@*METHODS@#The stable T-ALL cell line with knocked down β-arrestin1 (Jurkat Siβ1) was constructed. Flow cytometry and probe assays were used to detect ROS content in cell and mitochondrial, respectively. The relationship between β-arrestin1 and microRNA was detected, analyzed and Q-PCR confirmed by microRNA microarray. The target genes of microRNA were predicated by miRbase software, identified by Western blot, and validated by Dual luciferase reporter gene.@*RESULTS@#Jurkat Siβ1 stable cell line was successfully constructed and it was found that ROS content was slightly reduced in Jurkat Siβ1 at the whole cell level, and the ROS content was also significantly reduced in mitochondria. MicroRNA microarray analysis revealed that multiple T-ALL related microRNAs showed differentially expressed, in which the expression of miR-652-5p was significantly increased in Jurkat Siβ1 (P2.0), and Q-PCR showed that miR-652-5p was nearly 5-fold up-regulated in Jurkat Siβ1. miRbase predicted that the P62 gene was the target gene of miR-652-5p which could regulates mitochondrial function. P62 protein showed highly expressed in stably knocked down miR-652-5p in Jurkat cells. Dual luciferase reporter gene assay confirms that P62 was the target gene of miR-652-5p.@*CONCLUSION@#β-arrestin1 can decreases the expression of miR-652-5p and deregulates the translational inhibition of P62 mRNA, thus to increase ROS content in mitochondria of T-ALL cells.


Subject(s)
Humans , MicroRNAs/genetics , Mitochondria , Oxygen , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , RNA, Messenger , beta-Arrestin 1
6.
Journal of Experimental Hematology ; (6): 1101-1108, 2021.
Article in Chinese | WPRIM | ID: wpr-888524

ABSTRACT

OBJECTIVE@#To screen the core genes of Philadelphia chromosome positive/Ph like T-cell acute lymphoblastic leukemia (Ph@*METHODS@#The WES/RNA-seq examination results of Ph@*RESULTS@#For Ph@*CONCLUSION@#There are obviously abnormal DNA damage repair pathways in children with Ph


Subject(s)
Child , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Humans , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Signal Transduction , Software
7.
Hematol., Transfus. Cell Ther. (Impr.) ; 42(4): 320-325, Oct.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142974

ABSTRACT

ABSTRACT Background and objective T-cell acute lymphoblastic leukemia (T-ALL) in children represents a high-risk disease. There is a lack of studies assessing the outcome of T-ALL in Hispanic populations, in which it is a rare malignancy. We report the characteristics and results of treatment for childhood T-cell ALL in children over 14 years at a Latin American reference center. Material and methods From January 2005 to December 2018, there occurred the analysis of twenty patients ≤ 16 years of age from a low-income open population diagnosed at a university hospital in Northeast Mexico. Clinical and laboratory characteristics, treatment regimens and outcomes were assessed by scrutinizing clinical records and electronic databases. Diagnosis was confirmed by flow cytometry, including positivity for CD-2, 5, 7 and surface/cytoplasmic CD3. Survival rates were assessed by the Kaplan-Meier method. Results There was a male preponderance (70 %), with a 2.3 male-to-female ratio (p= .074), the median age being 9.5 years. Leucocytes at diagnosis were ≥ 50 × 109/L in 13 (65 %) children, with CNS infiltration in 6 (30 %) and organomegaly in 10 (50 %). The five-year overall survival (OS) was 44.3 % (95 % CI 41.96-46.62), significantly lower in girls, at 20.8 % (95 % CI 17.32-24.51) vs. 53.1 % (95 % CI 50.30-55.82), (p= .035) in boys; there was no sex difference in the event-free survival (EFS) (p= .215). The survival was significantly higher after 2010 (p= .034). Conclusion The T-cell ALL was more frequent in boys, had a higher mortality in girls and the survival has increased over the last decade with improved chemotherapy and supportive care.


Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Sex Distribution , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Child
8.
J. pediatr. (Rio J.) ; 96(1): 108-116, Jan.-Feb. 2020. tab, graf
Article in English | LILACS | ID: biblio-1090992

ABSTRACT

Abstract Objective Acute lymphoblastic leukemia is the most common childhood cancer, yet surprisingly, very few studies have reported the treatment outcomes and the relapse rate of patients from low/middle-income countries. Method This study was a 5-year retrospective cohort study. It was conducted at Oncology Center of Mansoura University in Egypt and aimed to estimate the treatment outcomes and the relapse rates of newly diagnosed acute lymphoblastic leukemia in children. Results Two hundred children suffering from acute lymphoblastic leukemia were studied; forty-six patients (23%) died during induction and most of those deaths were related to infection. Forty-one patients (27%) relapsed out of the 152 patients who achieved complete remission. The most common site of relapse was the bone marrow, followed by the isolated central nervous system, 53.7% and 31.7%, respectively. Seventy-eight percent of relapses occurred very early/early rather than later. The majority of relapse patients' deaths were related to infection and disease progression. The 5-year overall survival rate for patients was 63.1% (82.1% for non-relapsed compared to 36.6% for relapsed patients). Conclusion There was a high incidence of induction deaths related to infection and high percentages of very early/early relapses, with high mortalities and low 5-year overall survival rates. These findings suggest the urgent need for modification of chemotherapy regimens to be suitable for the local conditions, including implementation of supportive care and infection control policies. There is also a requirement for antimicrobial prophylaxis during induction period combined with the necessary increase in government healthcare spending to improve the survival of acute lymphoblastic leukemia in Egyptian children.


Resumo Objetivo Estimar os desfechos do tratamento e as taxas de recidiva de crianças recém-diagnosticadas com leucemia linfoblástica aguda. É o câncer infantil mais comum, mas surpreendentemente poucos estudos relataram os desfechos do tratamento e a taxa de recidiva em pacientes de países de renda baixa/média. Método Estudo de coorte retrospectivo de cinco anos. Foi feito no Centro de Oncologia da Universidade de Mansoura, no Egito. Resultados Foram estudadas 200 crianças com leucemia linfoblástica aguda, das quais 46 (23%) morreram durante a indução e a maioria dessas mortes estava relacionada à infecção. Dos 152 pacientes que alcançaram a remissão completa, 41 (27%) apresentaram recidiva. O local mais comum de recidiva foi a medula óssea, seguido pelo sistema nervoso central isolado, com 53,7% e 31,7% dos casos, respectivamente. Das recidivas, 78% ocorreram muito precocemente ou precocemente, em vez de tardiamente. A maioria das mortes de pacientes com recidiva estava relacionada à infecção e progressão da doença. A taxa de sobrevida global em cinco anos para os pacientes foi de 63,1% (82,1% para não recidivados em comparação com 36,6% para os recidivados). Conclusão Houve uma alta incidência de mortes na indução relacionadas à infecção e altos percentuais de recidivas muito precoces ou precoces, com altas taxas de mortalidade e baixas taxas de sobrevida global em cinco anos. Nossos achados sugerem a necessidade urgente de modificação dos esquemas quimioterápicos para adequação às nossas condições locais, implantação de políticas de cuidados de suporte e controle de infecções. Há também a necessidade de profilaxia antimicrobiana durante o período de indução, junto com um aumento necessário nos gastos governamentais com a saúde, para melhorar a capacidade de sobrevivência das crianças egípcias com leucemia linfoblástica aguda.


Subject(s)
Humans , Child , Developing Countries , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/therapy , Recurrence , Remission Induction , Survival Rate , Retrospective Studies , Treatment Outcome , Egypt
9.
Article in Chinese | WPRIM | ID: wpr-829047

ABSTRACT

OBJECTIVE@#To investigate the effects of dihydroartemisinin (DHA) on the proliferation and apoptosis of human T-cell acute lymphoblastic leukemia (T-ALL) Jurkat cell.@*METHODS@#The effects of DHA on the proliferation of Jurkat cells and the recovery of DHA-inhibited cell viability by N-acetyl-L-cysteine (NAC) were examined by CCK-8 assay. Flow cytometry was performed to analyze the cell apoptosis and generation of reactive oxygen species (ROS). Western-blot was used to detected protein expression of DNA damage-related genes, as well as apoptosis-associated genes, respectively.@*RESULTS@#DHA inhibited the proliferation of Jurkat cells, and shows a concentration-dependent manner(r =0.936), and NAC could partially restore the activity of DHA on cell proliferation inhibition. With the increase of drug concentration, the apoptosis rate (r =0.946) and ROS accumulation was increased (r =0.965). Western blot showed that the protein expressions of DNA damage-related gene γ-H2AX and apoptosis-related genes p53, c-Caspase3, BAX and cPARP were significantly increased, and BCL-2 protein expression was decreased.@*CONCLUSION@#DHA can induce ROS production in Jurkat cells, which can cause DNA damage, activate the P53 apoptotic pathway, and promote apoptosis of cells.


Subject(s)
Apoptosis , Artemisinins , Humans , Jurkat Cells , Oxidative Stress , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Reactive Oxygen Species
10.
Journal of Experimental Hematology ; (6): 1791-1795, 2020.
Article in Chinese | WPRIM | ID: wpr-879973

ABSTRACT

OBJECTIVE@#To analyze the characteristics of gene mutation in adult ALL and its clinical significance.@*METHODS@#Clinical data of 134 primary adult ALL patients and DNA sequencing results of 16 kinds of gene mutation were collected. The characteristic of gene mutation and clinical significances were statistically analyzed.@*RESULTS@#In 31 cases of 134 ALL cases (23.13%) the gene mutations were detected as follows: 19 cases of 114 B-ALL cases (16.67%), 11 cases of 19 T-ALL cases (57.89%) and 1 case of T/B-ALL. The incidence of T-ALL gene mutation was significantly higher than that of B-ALL (χ@*CONCLUSION@#There may be multiple gene mutations in adult ALL patients. IL7R and NOTCH1 are the most common gene mutations and NOTCH1 mutation may indicate poor prognosis. Detection of gene mutations is helpful to understand the pathogenesis of ALL and evaluate the prognosis of adult ALL patients.


Subject(s)
Adult , Humans , Mutation , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Receptor, Notch1/genetics , Sequence Analysis, DNA
11.
San Salvador; s.n; 2020. 62 p. graf.
Thesis in Spanish | LILACS, BISSAL | ID: biblio-1150828

ABSTRACT

La leucemia aguda es la primera causa de cáncer en niños menores de 15 años en el mundo, siendo la leucemia linfoblástica aguda (LLA), la malignidad pediátrica más común, existe una clasificación de riesgo de pacientes que se someten a quimioterapia, catalogándolos como de Alto, Estándar y Bajo riesgo, siguiendo, de acuerdo a estándares internacionales, 3 fases de tratamiento, que son: Inducción, Consolidación y Mantenimiento. En el análisis del protocolo AHOPCA LLA 2015, la muerte por inducción es de un 3%. Se define como evento adverso a aquel evento que se ve relacionado con el perfil de toxicidad de la droga quimioterapéutica usada en determinada fase de tratamiento, siendo más frecuentes en la fase de inducción, y con mayor potencial de mortalidad. Dichos eventos adversos se reportan mediante la escala CTCAE (Common terminology criteria for adverse events), en grados del 0 al 5. El objetivo principal del presente estudio es estimar la prevalencia de eventos adversos grados 3,4 y 5, según escala CTACE, asociados a quimioterapia de inducción, en pacientes con diagnóstico de Leucemia Linfoblástica Aguda, atendidos en el Hospital Nacional de Niños Benjamín Bloom, mayo 2016 ­ mayo 2017. Mediante un estudio descriptivo y retrospectivo, de 73 pacientes, el presente trabajo determinó un porcentaje de eventos adversos en pacientes con LLA en quimioterapia de inducción del 35.6%, con una prevalencia en pacientes con LLA con enfermedad activa recibiendo quimioterapia del 6%, siendo los eventos adversos infecciosos los más frecuentes con un 40%, seguidos de los eventos trombóticos no cerebrales y hepatobiliares con un 13.33%. Según gravedad por escala CTCAE, fueron más frecuentes los eventos grado 3 con un 73.3%. Un 42.3% de pacientes con eventos adversos presentó enfermedad de Riesgo Alto y Moderado, observándose una mortalidad del 4.1%


Subject(s)
Drug Therapy , Pediatrics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
12.
Oncol. (Guayaquil) ; 29(2): 127-136, 30 de Agosto del 2019.
Article in Spanish | LILACS | ID: biblio-1015459

ABSTRACT

Introducción: Las leucemias linfoblásticas agudas (LLA) son proliferaciones clónales malignas de células en distintos grados de diferenciación y representan las neoplasias más frecuentes en la edad pediátrica. El objetivo de este estudio es determinar las principales características inmunofenotípicas, biológicas y moleculares de las LLA en nuestro medio. Métodos: Se realiza un estudio retrospectivo, de tipo no experimental, descriptivo, y longitudinal de los pacientes diagnosticados de LLA durante el periodo comprendido entre 2004 a 2009 en el Instituto Oncológico Nacional "Dr. Juan Tanca Marengo" Solca, Guayaquil. Resultados: Se analizaron un total de 316 pacientes, con una edad promedio de 6 años. Por sus características morfológicas fueron clasificados como FAB L1 en 90.5 % de los casos (n=286). En base a su inmunofenotipo 91.8 % (n=290) de los mismos correspondieron a una LLA de fenotipo B y un 8.2 % (n=26) a una de fenotipo T, el con un predominio de la variedad B común. Se reportaron 45 casos de translocaciones, siendo a más común la t(12;21). En relación al cariotipo este se reportó como normal en 229 casos (72.5 %) y se evidenciaron gran variabilidad de alteraciones en el restante 27.5 %, prevaleciendo las hiperdiploidías. Conclusión: Una mejor clasificación y estatificación de los pacientes, por medio de la correlación de los hallazgos inmunofenotípicos, morfológicos y citogenéticos permitirá establecer nuevas estrategias terapéuticas con una mejor sobrevida.


Introduction: Acute lymphoblastic leukemias (ALL) are malignant clonic proliferations of cells at different degrees of differentiation and represent the most frequent neoplasms in pediatric age. The objective of this study is to determine the main immunophenotypic, biological and molecular characteristics of ALL in our environment. Methods: A retrospective, non-experimental, descriptive and longitudinal study of patients diagnosed with ALL during the period between 2004 and 2009 is carried out in the pediatric area of the National Oncology Institute "Dr. Juan Tanca Marengo "Solca, Guayaquil. Results: A total of 316 patients were analyzed, with an average age of 6 years. Due to their morphological characteristics, they were classified as FAB L1 in 90.5% of cases (n = 286). According to their immunophenotype, 91.8% (n = 290) of them corresponded to an ALL of the phenotype B and 8.2% (n = 26) to one of the phenotype T, with a predominance of the common variety B. 45 cases of translocations, the most common being t (12; 21). In relation to the karyotype, this was reported as normal in 229 cases (72.5%) and there was a great variability in the alterations in the rest of 27.5%, with hyperdiploidías prevailing. Conclusion: A better classification and staging of patients, through the correlation of immunophenotypic, morphological and cytogenetic findings, will allow the establishment of new therapeutic strategies with better survival.


Subject(s)
Humans , Leukemia, Biphenotypic, Acute , Cytogenetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Neprilysin , Fluorescent Antibody Technique, Indirect , Cytotoxicity, Immunologic
13.
Article in Chinese | WPRIM | ID: wpr-771900

ABSTRACT

OBJECTIVE@#To identify the differentially expressed gene (DEG) core genes in early T-cell precursor acute lymphoblastic leukemia (ETP ALL) and to analyze their interactions with upstream miRNAs, lncRNAs and involved pathways; to clarify the regulatory mechanism of ETP ALL development; and to explore the molecular targets for clinical diagnosis and treatment.@*METHODS@#The DEG of ETP ALL were screened based on the intersection of GEO database and TCGA database. The functional enrichment analysis and interaction analysis were carried out for DEG. Next, MCODE algorithm was used to screen core genes of DEG, and the mirDIP online tool and starBase online tool were utilized to predict upstream miRNA and lncRNA of the core genes.@*RESULTS@#A total of 424 DEG with a high credibility were identified, which were mainly enriched in the biological activity, such as transcriptional regulation, signaling pathway and protein function activation according to GO function, and the KEGG pathway was enriched in hematopoiesis, anoxic stress response, transcriptional misregulation, immunity and other functions, which interrelated each other 7 core genes were identified. Subsequently, 7 miRNAs and 19 lncRNAs were predicted to meet screening criteria. Finally, a lncRNA-miRNA-mRNA-pathway regulatory network was constructed.@*CONCLUSION@#The DEG in ETP ALL has been identified based on data mining methods; the core genes have been gained by co-expression analysis, and their upstream miRNA and lncRNA can be predicted for the early diagnosis of ETP ALL, thus providing a theoretical basis for the early diagnosis and reasonable treatment of ETP ALL, and helping to look for new tumor biomarkers of ETP ALL different from classical T-ALL.


Subject(s)
Humans , MicroRNAs , Precursor Cells, T-Lymphoid , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , RNA, Long Noncoding , RNA, Messenger
14.
Article in English | WPRIM | ID: wpr-763032

ABSTRACT

Nitrogen-containing heterocycles such as quinoline, quinazolinones and indole are scaffolds of natural products and have broad biological effects. During the last years those structures have been intensively synthesized and modified to yield new synthetic molecules that can specifically inhibit the activity of dysregulated protein kinases in cancer cells. Herein, a series of newly synthesized isoquinolinamine (FX-1 to 8) and isoindoloquinazolinone (FX-9, FX-42, FX-43) compounds were evaluated in regards to their anti-leukemic potential on human B- and T-acute lymphoblastic leukemia (ALL) cells. Several biological effects were observed. B-ALL cells (SEM, RS4;11) were more sensitive against isoquinolinamine compounds than T-ALL cells (Jurkat, CEM). In SEM cells, metabolic activity decreased with 10 μM up to 26.7% (FX-3), 25.2% (FX-7) and 14.5% (FX-8). The 3-(p-Tolyl) isoquinolin-1-amine FX-9 was the most effective agent against B- and T-ALL cells with IC50 values ranging from 0.54 to 1.94 μM. None of the tested compounds displayed hemolysis on erythrocytes or cytotoxicity against healthy leukocytes. Anti-proliferative effect of FX-9 was associated with changes in cell morphology and apoptosis induction. Further, influence of FX-9 on PI3K/AKT, MAPK and JAK/STAT signaling was detected but was heterogeneous. Functional inhibition testing of 58 kinases revealed no specific inhibitory activity among cancer-related kinases. In conclusion, FX-9 displays significant antileukemic activity in B- and T-ALL cells and should be further evaluated in regards to the mechanisms of action. Further compounds of the current series might serve as templates for the design of new compounds and as basic structures for modification approaches.


Subject(s)
Apoptosis , Biological Products , Erythrocytes , Hemolysis , Humans , Inhibitory Concentration 50 , Leukocytes , Phosphotransferases , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Protein Kinases , Quinazolinones
15.
Article in Chinese | WPRIM | ID: wpr-776006

ABSTRACT

To analyze the treatment and prognosis of T cell acute lymphoblastic leukemia(T-ALL)in adults. Method The clinicobiogical and survival data of 68 adult patients with newly diagnosis T-ALL were retrospectively analzyed. Results The median age of these 68 patients was 23 years(14-60 years).T-ALL was more common in men(81%).After the first cycle of treatment,complete remission was achieved in 50 patients(73%).The highest complete remission(CR) rate was in patients with cortex T-ALL(100%),followed by other T-ALL(73%)and early T-cell precursor lymphoblastic leukemia(54%),(=5.712,=0.058).The CR rate for adults aged >35 years was significantly lower than that of patients aged ≤ 35 years(40% 79%,=6.364,=0.012).The overall CR rate after the second treatment course was 93%.For patients treated with chemotherapy,autograft hematopoietic stem cell transplantation(auto-SCT),and allogeneic SCT,the median relapse free survival was 10 months,24 months,and not reached,respectively(=0.002).The 5-year overall survival rate was 25% for all patients;for patients treated with chemotherapy,auto-SCT and allogeneic SCT,the median overall survival was 24 months,34 months,and 30 months,respectively(=0.007),and the 5-year overall survival rate was 9%,33%,and 38%(=0.037).Multivariate analysis showed leukocyte count ≥100×10 /L was a risk factor for decreased relapse free survival(risk ratio 2.540,95%=1.058-6.099,=0.037). Conclusion Adult T-ALL patients have poor prognosis,which may be improved by SCT.


Subject(s)
Adolescent , Adult , Disease-Free Survival , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Diagnosis , Therapeutics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Diagnosis , Therapeutics , Prognosis , Remission Induction , Retrospective Studies , Survival Rate , Treatment Outcome , Young Adult
16.
Journal of Experimental Hematology ; (6): 1344-1347, 2019.
Article in Chinese | WPRIM | ID: wpr-775716

ABSTRACT

Abstract  Numerous studies have confirmed that abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway is one of the most common induction mechanisms of T-ALL. In recent years, many literature report that multiple abnormally expressed microRNAs (miRNAs) can participate in the development of T-ALL by regulating the PI3K/AKT signaling pathway. For example, overexpression of miR-19 and miR181a can activate the PI3K/AKT signaling pathway, which leads to the development of T-ALL and induction of chemotherapy drug resistance, as well as the low expression of miR-26b and miR-29a. Apart from the inhibitors and traditional Chinese medicines that target the PI3K/AKT signaling pathway, regulation of the expression of the corresponding miRNA may also be a potential treatment protocol for T-ALL. The mechanisms of PI3K/AKT signaling pathway involved in the development of T-ALL, the role of miRNAs in the PI3K/AKT signaling pathway and the targeted therapy based on this signaling pathway are summarized briefly in this review.


Subject(s)
Humans , Leukemia, T-Cell , MicroRNAs , Phosphatidylinositol 3-Kinases , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Proto-Oncogene Proteins c-akt , Signal Transduction
17.
Journal of Experimental Hematology ; (6): 1449-1454, 2019.
Article in Chinese | WPRIM | ID: wpr-775700

ABSTRACT

OBJECTIVE@#To analyze and investigate the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with T cell acute lymphoblastic leukemia (T-ALL) and their significance.@*METHODS@#Sixty patients with T-ALL and 60 patients with acute myelogenous leukemia (AML) diagnosed in our hospital from June 2012 to March 2015 were enrolled in T-ALL group and AML group, respectively. Another 30 healthy people were enrolled in the control group. Peripheral blood was collected to detect the expression levels of HES1, C-MYC and NF-kB by RT-PCR. The general data and the expression of HES1, C-MYC and NF-kB in peripheral blood were compared among the patients with different type of leukemia, cytogenetical types and different prognosis.@*RESULTS@#There was no significant difference in baseline data, such as age and sex among the 3 groups (P>0.05). The Hb level, WBC and Plt count, BM blast cell ratio in T-ALL and AML groups all were significantly higher than those in control group (P<0.01), but there were no statistical difference in above-mentioned indicators between T-ALL and AML groups (P>0.05). The expression levels of HES1, C-MYC and NF-kB in peripheral blood among 3 groups were significantly differenct (P<0.01), the expressions levels of HES1, C-MYC and NF-kB in T-ALL and AML groups were significantly higher than those in control were significantly group (P<0.01), moreover, the expression levels of above-mentional indicators in T-ALL groups were significantly higher than than those in AML group (P<0.01). The expression levels of HES1, C-MYC and NF-kB iin T-ALL patients with poor prognosis were significantly higher than those in T-ALL patients with favorable prognosis (P<0.01); the expression levels of HES1, C-MYC and NF-kB in peripheral blood of patients with different theraptic efficacy were follow: complete remission group<partial remission group<no remission group (P<0.01).@*CONCLUSION@#The HES1, C-MYC and NF-kB are highly expressed in peripheral blood of the patients with T-ALL, moreover, the expression levels maybe different, because of the cytogenetic, and theraptic efficacy.


Subject(s)
Humans , Leukemia, Myeloid, Acute , NF-kappa B , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Remission Induction , T-Lymphocytes , Transcription Factor HES-1
20.
Article in English | WPRIM | ID: wpr-717645

ABSTRACT

BACKGROUND: Precursor T-cell acute lymphoblastic leukemia (T-ALL) has worse prognosis than B-cell ALL. We aimed to evaluate prognostic variables in pediatric T-ALL. METHODS: Medical records of 36 T-ALL patients (27 males and 9 females; median age at diagnosis, 10.6 years) diagnosed and treated at Asan Medical Center from 2001 to 2017 were reviewed. Six patients (16.7%) had early T-cell precursor ALL (ETP-ALL). Most patients received the Children's Cancer Group-1882 (CCG1882) or Korean multicenter high risk ALL (ALL0601) protocols and prophylactic cranial irradiation. Clinical features at presentation, response to therapy, and treatment outcomes were analyzed. RESULTS: The six patients with ETP-ALL and 17 of 30 with non-ETP-ALL received CCG1882 or ALL0601 chemotherapy. Three patients, including two with ETP-ALL, did not achieve complete remission after induction. Rapid early response during induction was achieved by 26 patients. Five year overall survival (OS) and event free survival (EFS) rates were 71.4% and 70.2%, respectively. ETP-ALL and slow early response during induction were significant adverse prognostic factors, while hyperleukocytosis at diagnosis was not. CCG1882/ALL0601 chemotherapy resulted in superior survival (OS: 78.9%, EFS: 73.3%) compared with CCG1901 chemotherapy (OS: 64.3%, EFS: 64.3%), and patients undergoing prophylactic cranial irradiation had superior EFS to non-radiated patients. CONCLUSION: A high risk ALL protocol with intensified post-remission therapy, including prophylactic cranial irradiation, conferred T-ALL survival outcomes comparable with those of Western studies. Further treatment intensification should be considered for patients with ETP-ALL and slow induction responders. Additionally, CNS-directed treatment intensification, without prophylactic cranial irradiation, is needed.


Subject(s)
B-Lymphocytes , Cranial Irradiation , Diagnosis , Disease-Free Survival , Drug Therapy , Female , Humans , Male , Medical Records , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor Cells, T-Lymphoid , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , T-Lymphocytes
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