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1.
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
2.
Oncol. (Guayaquil) ; 30(1): 66-81, Abril. 2020.
Article in Spanish | LILACS | ID: biblio-1140886

ABSTRACT

Introducción: La leucemia linfoblásticaaguda (LLA) es una de las oncopatologías más frecuentes a nivel infantil, ocupando el primer lugar de los cincos tipos de cáncer con mayor incidencia en Ecuador. El objetivodel estudio fue determinar las frecuencias genotípicas y alélicas delos polimorfismos genéticos de MTHFR 677C>T (rs1801133) y MTHFR 1298A>C(rs1801131) en niños con leucemia linfoblástica aguda de SOLCA ­Loja y SOLCA ­Cuenca. Métodos:Es un estudio transversal, donde se evaluó a 160 pacientes pediátricosdiagnosticados con LLA. La detección de lospolimorfismos MTHFR 677C>T y 1298A>C se realizó mediante la técnica PCR entiempo real. El análisis estadístico descriptivo se desarrolló a través del software IBM SPSS (versión 22) y el programa bioinformático SNPStats. Resultados: Se determinóque las frecuencias genotípicas para el SNP MTHFR 677C>T fueron 25% C/C y 75%C/T con una frecuencia alélica del 38% para el alelo mutado (T). Para el SNP MTHFR1298 A>C se encontró una frecuencia genotípica de 2% A/A, 16% A/C y 82% C/C, entanto que su frecuencia alélica fue del 90% para el alelo mutado (C). No se encontróasociación genotípica ni alélica con ninguna de las variables intervinientes (p>0.05),así como tampoco se manifestó una correlación estadísticamente significativa de lospolimorfismos en mención y el tipo de riesgo de LLA. Conclusión:En la población estudiada con LLA, se evidenció para el SNP de MTHFR 677C>T una frecuencia genotípica del 75% para el heterocigoto C/T. Para el SNP MTHFR 1298A>C se encontró una frecuencia genotípica del 82% para el homocigoto mutado C/C. La distribución de la frecuencia alélica se mostró de la siguiente manera: para MTHFR 677C>T se obtuvo 38% para el alelo mutado T y en cuanto a MTHFR 1298 A>C, 90% correspondió para el alelo mutado C. En el análisis estadístico no se encontró asociación genotípica ni alélica con las variablesdemográficas y clínicas


Introduction:Acute lymphoblastic leukemia (ALL) is one of the most frequent oncopathologiesin childhood, occupying the first place of the five types of cancer with the highest incidence in Ecuador. The objective of the study was to determine the genotypic and allelic frequencies of the genetic polymorphisms of MTHFR 677C> T (rs1801133) and MTHFR 1298A> C (rs1801131) in children with acute lymphoblastic leukemia from SOLCA -Loja and SOLCA -Cuenca. Methods: It is a cross-sectional study, where 160 pediatric patients diagnosed with ALL were evaluated. The detection of MTHFR 677C> T and 1298A> C polymorphisms was performed using the real-time PCR technique. The descriptive statistical analysis was developed using the IBM SPSS software (version 22) and the SNPStats bioinformatics program. Results: It was determined that the genotype frequencies for the SNP MTHFR 677C> T were 25% C / C and 75% C / T with an allele frequency of 38% for the mutated allele (T). For the SNP MTHFR 1298 A> C, a genotype frequency of 2% A / A, 16% A / C and 82% C / C was found, while its allelic frequency was 90% for the mutated allele (C). No genotypic or allelic association was found with any of the intervening variables (p> 0.05), as well as no statistically significant correlation of the mentioned polymorphisms and the type of risk of ALL. Conclusion: In the population studied with ALL, a genotypic frequency of 75% was evidenced for the MTHFR 677C> T SNP for the heterozygous C / T. For the SNP MTHFR 1298A> C, a genotypic frequency of 82% was found for the homozygous mutated C / C. The allelic frequency distribution was shown as follows: for MTHFR 677C> T, 38% was obtained for the mutated allele T and for MTHFR 1298 A> C, 90% corresponded to the mutated allele C. In the statistical analysis No genotypic or allelic association was found with demographic and clinical variables


Subject(s)
Humans , Polymorphism, Genetic , Leukemia, Biphenotypic, Acute , Precursor Cell Lymphoblastic Leukemia-Lymphoma
3.
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
5.
Blood Research ; : 63-73, 2019.
Article in English | WPRIM | ID: wpr-739432

ABSTRACT

BACKGROUND: Acute leukemia (AL), not clearly assigned to myeloid, B-lymphoid, or T-lymphoid lineage, is classified as either biphenotypic acute leukemia (BAL) based on the European Group for Immunological Classification of Leukemias (EGIL) or acute leukemia of ambiguous lineage (ALAL) encompassing acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemia (MPAL) based on the World Health Organization (WHO) criteria. METHODS: Medical records of children newly diagnosed with BAL or ALAL, based on the EGIL or the 2008/2016 WHO criteria, respectively, admitted at Chonnam National University Hospital in 2001–2017 were retrospectively reviewed. RESULTS: Twelve (3.2%) of 377 AL patients satisfied the BAL or ALAL definitions based on the EGIL or the WHO criteria, respectively. Among 12 patients including 11 with BAL and another with undefined case based on the EGIL criteria, 7 (1.9%) had ALAL based on more stringent 2016 WHO criteria (AUL, 2; MPAL, 5). One patient had MPAL with t(9;22)(q34;q11.2), BCR-ABL+, and two had MLL gene abnormality. ALL-directed regimen was associated with better complete remission rate compared with AML-directed regimen (100.0% vs. 16.7%; P=0.015). The 5-year overall survival (OS) and event-free survival (EFS) were 51.1±15.8% and 51.9±15.7%, respectively. AUL was associated with poor OS and EFS compared with MPAL (0.0% vs. 75.0±21.7%; P=0.008). CONCLUSION: Due to the rarity of the cases, future multicenter, prospective studies incorporating large number of cases are urgently warranted to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.


Subject(s)
Child , Classification , Disease-Free Survival , Humans , Immunophenotyping , Leukemia , Leukemia, Biphenotypic, Acute , Medical Records , Prognosis , Prospective Studies , Retrospective Studies , World Health Organization
6.
Rev. cuba. hematol. inmunol. hemoter ; 33(3): 95-101, jul.-set. 2017. ilus, tab
Article in Spanish | LILACS | ID: biblio-960425

ABSTRACT

Las leucemias agudas representan un grupo heterogéneo de hemopatías malignas que pueden ser de origen linfoide o mieloide en dependencia del clon celular que da lugar al proceso maligno. Sin embargo, existen casos de leucemias agudas con fenotipo mixto donde coexisten características propias de más de un linaje celular y que se conocen hoy como leucemias agudas de fenotipo mixto. Se presenta el caso de un paciente que se diagnosticó como una leucemia aguda híbrida linfoide B/mieloide mediante citometría de flujo. Se encontró la presencia del gen de fusión E2A-PBX1 que se forma como consecuencia de una traslocación entre los cromosomas 1 y 19. El paciente, un niño de 20 meses de nacido, falleció a los 12 días de iniciados los primeros síntomas clínicos. Se conoce que esta anormalidad cromosómica está asociada a un pronóstico desfavorable, principalmente por la grave afectación del sistema nervioso central como en efecto ocurrió. Hasta donde se alcanzó a revisar, no se encontró un reporte similar en la literatura de una leucemia aguda híbrida linfoide B/mieloide positiva al gen defusión E2A-PBX1(AU)


The acute leukemias are an heterogenous group of malignant hemopathies diseases characterized by excessive proliferation of an inmature cellular clon. Depending of the myeloid or lymphoid origin of such clon, the acute leukemia could be classified in myeloid or lymphoid respectivement. However, there are cases of acute leukemias with mixed phenotype where immunologic markers of more than on elineage are present. In the patient of this report was founded a mixed immunophenotype pattern by flow cytometry and the entity was classified as acute hybrid lymphoid B/ mieloid leukemia. Basedon theinicial diagnostic of acutelymphoidleukemia, the molecular studydiscoveredthepresence of E2A-PBX1 fusion gen. That molecular anomaly is formed as consequence of a traslocation between the1 and 19 chromosomes. The patient, a child of 20 months, died 12 days afte rthe first clynic symptoms begining. E2A-PBX1 fusion gen is associated to unfavorable outcome, mainly because the severe damage at the central nervous system as in fact it occurred. Until it was possible review, no any similar report was founded about a case of acute hybrid lymphoidB/myeloid leukemia positive to the E2A-PBX1 fusion gen(AU)


Subject(s)
Humans , Male , Infant , Leukemia, Biphenotypic, Acute/complications , Leukemia, Biphenotypic, Acute/diagnosis , Leukemia, Biphenotypic, Acute/immunology , Case Reports , Leukemia, Biphenotypic, Acute/mortality
7.
Rio de Janeiro; s.n; 2017. tab, graf, ilus.
Thesis in Portuguese | LILACS, Inca | ID: biblio-943742

ABSTRACT

A leucemia linfoblástica aguda de células precursoras B (LLA-CPB) é uma neoplasia heterogênea. Aproximadamente 60% das LLA-CPB apresentam alterações envolvendo o cromossomo 21, incluindo hiperdiploidia, fusão gênica ETV6‐UNX1 e amplificação intracromossomal do cromossomo 21 (iAMP21). Mecanismos epigenéticos contribuem para a leucemogênese e a metilação do DNA, por sua vez, pode ser modulada por polimorfismos na via do folato. Portanto, este estudo tem como objetivo caracterizar o perfil genético e de metilação de DNA em LLA-CPB com alterações no cromossomo 21. Este estudo partiu de uma série de 1006 casos de LLA-CPB diagnosticados de 2002-2016 e foi desenhado em 3fases: 1) Identificação dos casos com alterações em número de cópias (CNA) no cromossomo 21 usando multiplex ligation probe amplification (MLPA) e FISH (RUNX1 e sondas para os cromossomos 4, 8, 10, 14, 17, 18, X e Y); 2) Caracterização do perfil de metilação e CNA por meio da técnica de microarranjo. Para tanto, o DNA foi modificado com EZ DNA Methylation™ Kit e o perfil de metilação analisado pelo Infinium Human Methylation 450 BeadChip Kit; e 3) Análises comparativas de metilação de DNA gene-específica, metilação em LINE-1(pirosequenciamento) e genotipagem para o polimorfismo MTHFR rs1801133 (PCR-RFLP) entre os diferentes subtipos moleculares de LLA-CPB, controles e amostras em remissão. Encontramos evidências de ganhos em CNA no cromossomo 21 em 83/374 (22%) das amostras (MLPA)...


B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a heterogeneous disease. Approximately 60% of BCP-ALL present alterations involving chromosome 21 (chr 21), including high hyperdiploid, ETV6‐RUNX1 fusion and intrachromosomal amplification of thechromosome 21 (iAMP21). Contributing with this process, epigenetic mechanisms could regulate the transcription and induce leukemogenesis. Polymorphisms in genes involved in folate metabolism could influence this aberrant methylation. This study aimed to characterize the genetic and DNA methylation profile of BCP-ALL with chr 21 aberrations, as well as to identify the DNA methylation signatures of different BCP-ALL molecular subgroups. This study enrolled 1006 BCP-ALL diagnosed between 2002-2016 and was performed in tree steps: 1) Identification of copy number alterations (CNA) regarding the Chr 21 by multiplex ligation probe amplification (MLPA) and FISH (“LPH012 TEL/AML1 translocation, dual fusion probe and centromere probes to chr 4, 8, 10, 14, 17, 18, X and Y); 2) DNA methylation and CNAcharacterization by DNA methylation array. DNA from BCP-ALL cases, controls and remission samples was modified with EZ DNA Methylation™ Kit and analyzed by the InfiniumHumanMethylation450 BeadChip Kit; 3) Comparative gene methylation, LINE-1 methylation (pyrosequencing) and MTHFR rs1801133 genotype (PCR-RFLP) analysis between the different BCP-ALL subgroups. We found evidence of gains in chr 21 in 83/374 (22%) of the samples analyzed by MLPA. Among the BCP-ALL with chr 21 gains, 11/83 (13%) had ≥5 RUNX1 signals and 53/83 (64%) were classified as hyperdiploid...


Subject(s)
Humans , Male , Female , Child , Adolescent , Chromosomes, Human, Pair 21/genetics , Leukemia, Biphenotypic, Acute , DNA Methylation
8.
Rio de Janeiro; s.n; 2017. ilus, tab, graf.
Thesis in Portuguese | LILACS, Inca | ID: biblio-943740

ABSTRACT

Introdução: A leucemia linfoblástica aguda de células precursoras B (LLA-cpB) apresenta biomarcadores citogenético-moleculares clássicos com prognóstico bem definidos. Trinta por cento desses casos não possuem nenhuma dessas anormalidades e são referidas como B-others e 50% desse subgrupo possui perfil de expressão gênica semelhante a BCR-ABL1, sendo chamados então, de BCRABL1-like. Este subgrupo possui diferenças genéticas características como mutações nos genes JAK1/2, IL7Rα, e CRLF2, além da expressão gênica aumentada deste último. O CRLF2 forma um heterodímero com a cadeia alfa do receptor de Interleucina 7 (IL- 7Rα) ou CD127 formando o receptor da citocina TSLP. Estudos envolvendo o CRLF2 têm apresentado resultados controversos, devido a não utilização de técnicas padronizadas para sua detecção. Objetivo: Estabelecer um algoritmo de testes combinados imunofenotípicos e moleculares capazes de predizer o status do CRLF2 e sua associação com subtipos moleculares e celulares em amostras de crianças com LLA-cpB. Métodos: Análise do painel de anticorpos monoclonais CD10FITC/ CD127PE/CD45PerCP-CY5.5/ CD19PECY7 / CRLF2APC em 138 amostras de LLA-cpB ao diagnóstico (≤ 18 anos), quanto à expressão celular de CRLF2 e CD127 em blastos leucêmicos, avaliando percentual e intensidade mediana de fluorescência (IMF). Para avaliar a ploidia desses casos foi utilizado o índice de DNA por citometriade fluxo multiparamétrica (CFM) e a expressão gênica do CRLF2 foi avaliada por RTq-PCR. Já as alterações moleculares ETV6-RUNX1, E2A-PBX1, BCR-ABL1, r-KMT2A foram avaliadas por RTPCR. Para a avaliação da distribuição das variáveis categóricas foram aplicados os testes Exato de Fisher e Qui-Quadrado...


Introduction: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) presents classical cytogenetic molecular biomarkers with well-defined prognosis. Thirty percent of these cases do not have any of these abnormalities and are referred to as B-others and 50% of this subgroup has a BCRABL1similar gene expression profile, then called BCR-ABL1-like. This subgroup has characteristic genetic differences as mutations in the JAK1 / 2, IL7Rα, and CRLF2 genes, as well as increased geneexpression of the latter. CRLF2 forms a heterodimer with the alpha chain of the Interleukin 7 receptor (IL-7Rα) or CD127 forming the TSLP cytokine receptor. Studies involving the CRLF2 have presented controversial results due to the use of non-standardized techniques for their detection. Objective: To establish an algorithm of combined immunophenotypic and molecular tests capable of predicting the CRLF2 status and its association with molecular and cellular subtypes in children samples with BCPALL.Methods: Analysis of the monoclonal antibodies panel CD10FITC/CD127PE /CD45PerCPCY5.5 /CD19PE-CY7/ CRLF2APC in 138 samples of diagnostic-ALL (≤ 18 years) on cell expressionof CRLF2 and CD127 in leukemic blasts, evaluating percentage and median intensity of fluorescence (MIF). To evaluate the ploidy of these cases the DNA index was used by multiparametric flow cytometry (MFC) and the CRLF2 gene expression was evaluated by RTq-PCR. The molecular alterations ETV6-RUNX1, E2A-PBX1, BCR-ABL1, r-KMT2A were evaluated by RT-PCR. For theevaluation of the categorical variables distribution, Fisher's Exact and Qui-Square tests were applied. For the comparison of continuous variables, the non-parametric Mann-Whitney test (comparison of two groups) or Kruskal wallis (more than two groups) was used...


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Flow Cytometry , Gene Expression , Leukemia, Biphenotypic, Acute
9.
Rio de Janeiro; s.n; 2016. ilus.
Thesis in Portuguese | LILACS, Inca | ID: biblio-943269

ABSTRACT

Introdução: A leucemia linfoblástica aguda de células precursora B (LLA-CPB)pediátrica é caracterizada por alterações citogenético-moleculares recorrentes. Aamplificação intracromossomica do cromossomo 21 (iAMP21) tem sido descrita em 2-3% das LLA-CPB e foi associada a um maior risco de recaída. A técnica de FISH é ométodo universal para identificar a iAMP21 com sondas dirigidas para o gene RUNX1.A identificação da iAMP21 através de cópias adicionais de RUNX1 pode ocasionarresultados duvidosos. Foi demonstrado por análise genômica a presença de umaregião comum de amplificação (RCA) a qual estão presentes os genes GART,IFNGR2, DSCR1, DYRK1A, RUNX1, ERG e ETS2 em pacientes com iAMP21. Algunsdestes genes estão envolvidos na leucemogênese ou na resposta terapêutica deoutros subtipos de leucemia. Recentemente, sugerimos um grupo com perfil "iAMP21-like" (iAMP21-like). Além disso, as análises de FISH detectaram dois grupos com baseno ganho de cópias adicionais de RUNX1: 1) 3-4 sinais e 2) ≥ 5 sinais de RUNX1.Objetivo: Identificar genes potencialmente relevantes para a patogênese das LLACPBcom amplificações recorrentes no cromossomo 21. Metodologia: Aspirados demedula óssea (MO) de pacientes com LLA-CPB com amplificações recorrentes nocromossomo 21 (perfil iAMP21-like; 3-4 sinais RUNX1 e ≥5 sinais RUNX1), com afusão ETV6-RUNX1, sem fusões gênicas recorrentes, síndrome de Down (SD),hiperdiploidia com cópias do cromossomo 21 (HD+21) e um perfil normal docromossoma 21 pela técnica de MLPA foram submetidos à algumas análises. Aanálise da expressão gênica foi realizada por RT-qPCR. Os valores de fold-changeforam comparados entre os grupos de LLA-CPB tendo como controle uma amostracalibradoria do grupo controle MLPA normal. O número de cópias gênicas foideterminado por TaqMan Copy Number. A análise estatística foi realizada peloStudent’s t-test. As análises de correlação foram avaliadas pelo teste de Pearson...


Introduction: Childhood B-cell precursor acute is characterized by recurrent andmolecular alterations. The identification of these abnormalities is important for risk stratification therapeutic, and provides appropriate treatment. Intrachromosomal amplification of chromosome 21 (iAMP21) has been described in 2-3% of BCP-ALLand was associated with an increased risk of relapse. The FISH technique is the universal method for identifying iAMP21 using probes directed to RUNX1 gene. The identification of iAMP21 through additional copies of RUNX1 may cause unreliable results. It was demonstrated by genomic analysis the presence of common region ofamplification (RCA) which are present GART, IFNGR2, DSCR1, DYRK1A, RUNX1, ERG and ETS2 genes in iAMP21 patients. Some of these genes are involved in leukemogenesis or other therapeutic response leukemia subtypes. Recently, we suggest a group "iAMP21-like" profile (iAMP21-like). In addition, FISH analysis detected two groups based on the gain additional copies of RUNX1: 1) 3-4 signalsRUNX1 and 2) ≥ 5 signals RUNX1. Objective: To identify potentially relevant genes to the pathogenesis of BCP-ALL with recurrent amplifications on chromosome 21. Methodology: Bone marrow aspirates (BM) of BCP-ALL patients with recurrentamplifications on chromosome 21 (iAMP21-like profile, 3-4 signals RUNX1 and ≥5 signals RUNX1) with ETV6-RUNX1 fusion, without recurring gene fusions, Down syndrome (SD), hyperdiploidy with copies of chromosome 21 (HD+21), a normalprofile for MLPA chromosome 21 underwent the analysis. Gene expression analysis was performed by RT-qPCR. The fold-change values were compared between groups of BCP-ALL to a control sample calibradoria normal MLPA control group. The copynumber of the genes was performed by TaqMan Copy Number technique. Statistical analysis was performed by Student's t-test. Correlation analyzes were evaluated by Pearson test...


Subject(s)
Humans , Male , Female , Gene Expression , Genes , Leukemia, Biphenotypic, Acute
11.
Journal of Breast Cancer ; : 455-458, 2016.
Article in English | WPRIM | ID: wpr-28532

ABSTRACT

In acute leukemia, leukemic infiltration of the breast is extremely rare. We report a case of biphenotypic acute leukemia (BAL) that presented as a breast mass. A 30-year-old woman presented with a 4-month history of a right breast mass with nipple discharge and easy fatigue. She had received chemotherapy and peripheral blood stem cell transplantation for BAL and had been in complete remission for the last 2 years. Core needle biopsy of the breast mass revealed monomorphous infiltrates of blast cells with round nuclei and fine chromatin, consistent with leukemic infiltration. Subsequent bone marrow biopsy showed diffuse infiltration of immature cells. However, bone marrow karyotyping showed 46, XY, suggesting complete engraftment of transplanted donor cells. This is the report of BAL recurring as a breast mass. In the differential diagnosis of a breast mass, extramedullary relapse should be considered when the patient has a history of leukemia.


Subject(s)
Adult , Biopsy , Biopsy, Large-Core Needle , Bone Marrow , Breast , Chromatin , Diagnosis, Differential , Drug Therapy , Fatigue , Female , Humans , Karyotyping , Leukemia , Leukemia, Biphenotypic, Acute , Leukemic Infiltration , Nipples , Peripheral Blood Stem Cell Transplantation , Recurrence , Tissue Donors
12.
Braz. j. med. biol. res ; 48(10): 871-876, Oct. 2015. tab, ilus
Article in English | LILACS | ID: lil-761603

ABSTRACT

Treatments for patients with hematologic malignancies not in remission are limited, but a few clinical studies have investigated the effects of salvaged unrelated cord blood transplantation (CBT). We retrospectively studied 19 patients with acute leukemia, 5 with myelodysplastic syndrome (MDS with refractory anemia with excess blasts [RAEB]), and 2 with non-Hodgkin's lymphoma who received 1 CBT unit ≤2 loci human leukocyte antigen (HLA)-mismatched after undergoing myeloablative conditioning regimens between July 2005 and July 2014. All of them were in non-remission before transplantation. The infused total nucleated cell (TNC) dose was 4.07 (range 2.76-6.02)×107/kg and that of CD34+ stem cells was 2.08 (range 0.99-8.65)×105/kg. All patients were engrafted with neutrophils that exceeded 0.5×109/L on median day +17 (range 14-37 days) and had platelet counts of >20×109/L on median day +35 (range 17-70 days). Sixteen patients (61.5%) experienced pre-engraftment syndrome (PES), and six (23.1%) patients progressed to acute graft-versus-host disease (GVHD). The cumulative incidence rates of II-IV acute GVHD and chronic GVHD were 50% and 26.9%, respectively. After a median follow-up of 27 months (range 5-74), 14 patients survived and 3 relapsed. The estimated 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) rates were 50.5%, 40.3%, and 35.2%, respectively. Salvaged CBT might be a promising modality for treating hematologic malignancies, even in patients with a high leukemia burden.


Subject(s)
Adolescent , Adult , Child , Female , Humans , Male , Young Adult , Allografts , Anemia, Refractory, with Excess of Blasts/therapy , Cord Blood Stem Cell Transplantation , Graft vs Host Disease , Leukemia, Biphenotypic, Acute/therapy , Lymphoma, Non-Hodgkin/therapy , Anemia, Refractory, with Excess of Blasts/mortality , Cord Blood Stem Cell Transplantation/mortality , Disease-Free Survival , Follow-Up Studies , Graft vs Host Disease/mortality , Hematologic Neoplasms/mortality , Hematologic Neoplasms/therapy , Leukemia, Biphenotypic, Acute/mortality , Leukemia, Lymphoid/mortality , Leukemia, Lymphoid/therapy , Leukemia, Myeloid/mortality , Leukemia, Myeloid/therapy , Leukemia/mortality , Leukemia/therapy , Lymphoma, Non-Hodgkin/mortality , Myelodysplastic Syndromes/mortality , Myelodysplastic Syndromes/therapy , Retrospective Studies , Remission Induction/methods , Treatment Outcome
13.
Rev. bras. hematol. hemoter ; 37(4): 223-229, July-Aug. 2015. tab, ilus
Article in English | LILACS | ID: lil-756560

ABSTRACT

To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment.METHODS: Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.RESULTS: The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia...


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adolescent , Child , Leukemia, Biphenotypic, Acute , Leukemia, Lymphoid , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Survival Rate
14.
Cuad. Hosp. Clín ; 56(2): 45-48, 2015. ilus
Article in Spanish | LILACS | ID: biblio-972765

ABSTRACT

La leucemia bifenotípica aguda (LBA) es una enfermedad poco frecuente que comprende alrededor de 2 al 5% del total de casos de todas las leucemias. La LBA se caracteriza por la expresión asociada de 2 o más marcadores de diferentes líneas celulares en la población celular de blastos. Al respecto, la clasificación de neoplasias hematológicas y linfoides realizada por la OMS el 2008, incorporó los criterios de EGIL para el diagnóstico de este tipo de leucemia. La leucemia bifenotípica, que muestra fenotipos B y T es extremadamente rara y de mal pronóstico por lo que existe poca información respecto al manejo clínico de estos pacientes. Actualmente no existe un tratamiento estándar para estos casos, ya que no se pueden realizar estudios clínicos aleatorizados debido a la baja incidencia de la LBA. Sin embargo, el uso del protocolo Hiper CVAD (hiperfraccionamiento de ciclofosfamida, vincristina, adriamicina y dexametasona; y altas dosis de citarabina y metotrexato) ha logrado un 78% de remisión completa y una media de duración de sobrevivencia de 27 meses. Recientemente la incorporación de inhibidores de la tirosina kinasa (imatinib, nilotinib o dasatinib) en combinación con el protocolo hiperCVAD ha mejorado la tasa de remisión completa durante la inducción. En este trabajo reportamos el caso de un paciente diagnosticado con leucemia bifenotípica B/T cuya población clonal presentó positividad para marcadores linfoides, obteniéndose una puntuación de 6,5 para el linaje B y 4,5 para el linaje T según los criterios de EGIL.


Biphenotypic acute leukemia (BAL) is an uncommon disease comprising approximately from 2 to 5% of all leukemia cases. BAL is characterized by the associated expression of two or more markers of different cell lines in a single blasts population. In this regard, 2008 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues included EGIL score system for diagnosing this type of leukemia. The biphenotypic leukemia that expresses B and T phenotypes is extremely unusual and it has poor prognosis. Due to low incidence of BAL, it is not possible to conduct randomized trials and consequently little is known about the clinical management of this kind of patients. Currently, there is no a standard treatment for these cases. However, the use of Hyper-CVAD regimen (hyperfractionated of cyclophosphamide, vincristine, adriamycin, and dexamethasone; and high dose of methotrexate and cytarabine) has achieved a 78% of complete remission with an average survival of 27 months; and the incorporation of tyrosine kinase inhibitors (imatinib, nilotinib or dasatinib) has improved the remission rate during induction. We report the case of a patient whose clones gave positive for B and T lymphoid markers and according to EGIL score system, it was obtained 6.5 for B lineage and 4.5 for Tlineage


Subject(s)
Humans , Leukemia, Biphenotypic, Acute/diagnosis , Leukemia, Biphenotypic, Acute/prevention & control
15.
Odontol. pediatr. (Lima) ; 13(2): 104-110, jul.-dic.2014. tab, graf
Article in Spanish | LILACS, LIPECS | ID: lil-781603

ABSTRACT

Determinar la prevalencia de mucositis bucal en niños con leucemia linfoblástica aguda que reciben quimioterapia en el Hospital Edgardo Rebagliati Martins 2007-2011. Materiales y Métodos: Se realizó una investigación retrospectiva de los años 2007 al 2011. El estudio estuvo constituido por las historias clínicas de pacientes con diagnóstico de leucemia linfoblástica aguda del Servicio de Hematología Pediátrica de 1 a 14 años y 11 meses. Los datos fueron recogidos en una ficha elaborada para ser analizados en una base de datos creadas para este fin. Resultados: De las 107 historias clínicas de pacientes con diagnóstico de leucemia linfoblástica aguda, 49 (45.8%) desarrollaron mucositis bucal. De estos 49 pacientes, corresponden al sexo masculino 25 (23.4%) y al femenino 24 (22.4%). El grado 1 de mucositis bucal se presentó con mayor frecuencia en el grupo de 1 a 5 años con 22 (84.6%) casos. El mayor porcentaje de neutropenia y leucocitosis se asoció a la leucemia linfoblástica aguda B en niños con un total de 57.9% y 57.5% respectivamente. Las enfermedades bucales asociadas a la quimioterapia con mayor frecuencia fueron aftas y candidiasis. Conclusión: La prevalencia de mucositis bucal es mayor en niños con leucemia linfoblástica aguda B en el grupo de 1 a 5 años...


To determine the prevalence of oral mucositis in children receiving chemotherapy for acute lymphoblastic leukemia in Edgardo Rebagliati Martins hospital, from 2007 to 2011. Materials and methods: A retrospective investigation was performed between 2007 y 2011. The study was comprised of the medical records of patients with acute lymphoblastic leukemia in the pediatric hematology department from 1 to 14 years and 11 month old. Data were collected on a card to be analyzed in a database created for this purpose. Results: Of the 107 medical records of patients with acute lymphoblastic leukemia, 49 (45.8%) developed oral mucositis. Of these 49 patients, correspond to males 25 (23.4%) and females 24 (22.4%). The oral mucositis grade 1 22 (84.6 %) was more frequently presented in the 0 to 5 years with 22 (84.6%) cases. The highest percentage of neutropenia and leukocytosis was associated with B acute lymphoblastic leukemia in children with an absolute of 92.5% and 91.3% respectively. Conclusion: The prevalence of oral mucositis is higher in children with acute lymphoblastic leukemia B, in the group of 1 -5 years...


Subject(s)
Humans , Child , Candidiasis, Oral , Stomatitis, Aphthous , Leukemia, Biphenotypic, Acute , Retrospective Studies , Peru
16.
Rev. bras. hematol. hemoter ; 36(5): 351-355, Sep-Oct/2014. tab, graf
Article in English | LILACS | ID: lil-725683

ABSTRACT

Objective: This study investigated the occurrence of the p190 and p210 break point clusterregion-Abelson (BCR-ABL) rearrangements in adults with acute lymphoblastic leukemia and possible associations with clinical and laboratory characteristics and survival. Methods: Forty-one over 18-year-old patients with acute lymphoblastic leukemia of both genders followed-up between January 2008 and May 2012 were included in this study. Clinical and laboratory data were obtained from the medical charts of the patients. Reverse transcription polymerase chain reaction (RT-PCR) using specific primers was employed to identify molecular rearrangements. Results: At diagnosis, the median age was 33 years, and there was a predominance of males (61%). The most common immunophenotype was B lineage (76%). BCR-ABL rearrangements was detected in 14 (34%) patients with the following distribution: p190 (28%), p210 (50%) and double positive (22%). Overall survival of patients with a mean/median of 331/246 days of follow up was 39%, respectively, negative BCR-ABL (44%) and positive BCR-ABL (28%). Conclusion: These results confirm the high frequency of BCR-ABL rearrangements and the low survival rate of adult Brazilian patients with acute lymphoblastic leukemia...


Subject(s)
Humans , Adult , Adult , Fusion Proteins, bcr-abl , Leukemia, Biphenotypic, Acute , Survival Analysis
17.
Rev. bras. hematol. hemoter ; 36(4): 293-296, Jul-Aug/2014. graf
Article in English | LILACS | ID: lil-718407

ABSTRACT

Mixed phenotype acute leukemia is a rare subtype of leukemia that probably arises from a hematopoietic pluripotent stem cell. The co-expression of two of myeloid, B- or T-lymphoid antigens is the hallmark of this disease. Herein, the case of a 28-year-old female patient is reported who presented with hemoglobin of 5.8 g/dL, white blood cell count of 138 × 109/L and platelet count of 12 × 109/L. The differential count of peripheral blood revealed 96% of blasts. Moreover, the patient presented with lymphadenopathy, splenomegaly and bone marrow infiltration by monocytoid blasts characterized as 7% positivity by Sudan Black cytochemical staining. Immunophenotyping revealed the involvement of blasts of both T- and monocytic lineages. The cytogenetic analysis showed an isolated 17p deletion. Thus, the diagnosis of T-cell/myeloid mixed phenotype acute leukemia was made with two particular rare features, that is, the monocytic differentiation and the 17p deletion as unique cytogenetic abnormalities. The possibility of concomitant expressions of T-cell and monocytic differentiation antigens in the same blast population is hard to explain using the classical model of hematopoiesis. However, recent studies have suggested that myeloid potential persists even when the lineage branches segregate toward B- and T-cells. The role of an isolated 17p deletion in the pathogenesis of this condition is unclear. At present, the patient is in complete remission after an allogeneic stem cell transplantation procedure...


Subject(s)
Humans , Female , Adult , Antigens , Antigens, Differentiation, Myelomonocytic , Chromosome Deletion , Flow Cytometry , Leukemia, Biphenotypic, Acute , Leukemia, Monocytic, Acute , Leukemia, Myeloid, Acute
18.
Chinese Medical Journal ; (24): 2999-3003, 2014.
Article in English | WPRIM | ID: wpr-318563

ABSTRACT

<p><b>OBJECTIVE</b>To highlight the current understanding of mixed phenotype acute leukemia (MPAL).</p><p><b>DATA SOURCES</b>We collected the relevant articles in PubMed (from 1985 to present), using the terms "mixed phenotype acute leukemia", "hybrid acute leukemia", "biphenotypic acute leukemia", and "mixed lineage leukemia". We also collected the relevant studies in WanFang Data base (from 2000 to present), using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".</p><p><b>STUDY SELECTION</b>We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version, with no limitation of research design. The duplicated articles are excluded.</p><p><b>RESULTS</b>MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously. The clinical manifestations of MPAL are similar to other acute leukemias. The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 criteria are most widely used. MPAL does not have a standard therapy regimen. Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features, and also the experience of individual physician. The lack of effective treatment contributes to an undesirable prognosis.</p><p><b>CONCLUSION</b>Our understanding about MPAL is still limited. The diagnostic criteria have not been unified. The treatment of MPAL remains to be investigated. The prognostic factor is largely unclear yet. A better diagnostic criteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.</p>


Subject(s)
Humans , Leukemia, Biphenotypic, Acute , Diagnosis , Metabolism , MicroRNAs , Metabolism
19.
Journal of Experimental Hematology ; (6): 1226-1229, 2014.
Article in Chinese | WPRIM | ID: wpr-302315

ABSTRACT

This study was aimed to explore the expression of CD34 in patients with biphenotypic acute leukemia (BAL) and its relation with the prognosis of BAL. The flow cytometry was used to detect leukemia-associated antigen. The used monoclonal antibodys (McAb) included CD10, CD19 and CD34 for B lymphocyte lineage, CD2, CD3 and CD5 for T lymohocyte lineage, MPO, CD13 and CD33 for myeloid lineage. The finally results were respectively analyzed. The results indicated that 9 out of 216 cases of leukemia was diagnosed as BAL (4.2%). Among 9 cases of BAL, 6 cases showed the common expression of myeloid and T lymohocyte lineages (66.7%), 3 cases showed the common expression of myeloid and B lymohocyte lineages (33.3%). 4 cases of BAL displayed CD34 positive expression (44.4%). As compared with acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL), the BAL patients showed higher CD34 positive expression (P < 0.05). It is concluded that the BAL patients show a poor prognosis, as compared with AML or ALL patients. The therapeutic effect of BAL may negatively correlate with the CD34 positive expression.


Subject(s)
Aged , Antigens, CD34 , Metabolism , Flow Cytometry , Humans , Immunophenotyping , Leukemia, Biphenotypic, Acute , Diagnosis , Metabolism , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis
20.
West Indian med. j ; 62(8): 701-704, Nov. 2013.
Article in English | LILACS | ID: biblio-1045736

ABSTRACT

PURPOSE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncologypatients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia. METHODS: We studied 18 cases of haematological malignancies which comprised five patients with TALL, 12 patients with AML and one with biphenotypic leukaemia. RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement. CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.


OBJETIVO: La detección de la clonalidad mediante amplificación de los reordenamientos del gen de la cadena pesada (IGH) de inmunoglobulina por reacción en cadena de la polimerasa (RCP) es una herramienta útil en el diagnóstico de varios tumores malignos linfoides de células B. El reordenamiento del gen de la cadena pesada de inmunoglobulina puede ser un objetivo óptimo de la detección de la clonalidad en tumores malignos linfoides de células B. En el presente estudio, se evaluó la presencia de reordenamiento del gen IGH en pacientes de hemato-oncología de células no B, incluyendo la leucemia linfoblástica aguda de células T (LLA-T), leucemia mieloblástica aguda (LMA), y leucemia bifenotípica. MÉTODOS: Se estudiaron 18 casos de neoplasias malignas hematológicas que abarcaron cinco pacientes con (LLA-T), 12pacientes con AML y uno con leucemia bifenotípica. CONCLUSIÓN: Reordenamiento del gen de la inmunoglobulina que ocurre en casi todas las neoplasias malignas hematológicas del linaje de las células B, también se presenta en una proporción muy pequeña de células T o las neoplasias mieloides.


Subject(s)
Humans , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Gene Rearrangement/genetics , Leukemia, Biphenotypic, Acute/genetics , Leukemia, Myeloid, Acute/genetics , Genes, Immunoglobulin Heavy Chain/genetics , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Polymerase Chain Reaction , Prospective Studies
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