ABSTRACT
La Leucemia Linfoblástica Aguda (LLA) es la neoplasia más frecuente en edad pediátrica. En los últimos años, entre el 15 y 20% de los pacientes fracasan en el tratamiento. Conocimientos en citogenética y biología molecular repercuten de manera importante en la determinación del pronóstico y del esquema de tratamiento adecuado. En Venezuela existe un conocimiento limitado en cuanto a la genética molecular de esta alteración onco-hematológica. El objetivo del trabajo fue evaluar las alteraciones genéticas más frecuentes en pacientes venezolanos con diagnóstico clínico de leucemia linfoblástica aguda. Se realizó un estudio transversal, descriptivo y prospectivo de 2006 a 2014, en el que se evaluaron las translocaciones ETV6/RUNX1, MLL/AF4, TCF3/PBX1, BCR/ABL1, así como las mutaciones en los genes PAX5 y FLT3 mediante el uso de diferentes tipos de PCR. Ciento treinta pacientes con diagnóstico clínico de leucemia linfocítica aguda fueron incluidos en el estudio. Se identificaron alteraciones moleculares en 56 pacientes (43,1%), en los que observamos la presencia de una o varias alteraciones en conjunción en un mismo paciente. Las alteraciones identificadas fueron t(12;21) (11,5%), t(4;11) (8,5%), t(1;19) (10%), t(9;22) (20,8%), ITD-FLT3 (14,8%), mutación P80S (4,2%) y S77del (4,2%) en el gen PAX5. La prevalencia de BCR/ ABL, es una de las más altas que ha sido descrita hasta ahora en casos de LLA donde la mayor parte de la población está conformada por pacientes pediátricos. Estos resultados representan el primer estudio molecular de la LLA en Venezuela, sentando las bases para el diagnóstico y seguimiento de la enfermedad en su población.
Acute Lymphoblastic Leukemia (ALL) is the most common neoplasm in pediatric age. In recent years, between 15 and 20% of patients failed in their treatments. Knowledge on cytogenetics and molecular biology has an important impact on the determination of the prognosis and the appropriate treatment scheme. In Venezuela there is limited knowledge regarding the molecular genetics of this onco-hematological alteration. The aim of this work was to evaluate the most frequent genetic alterations in Venezuelan patients with a clinical diagnosis of acute lymphoblastic leukemia. A cross-sectional, descriptive and prospective study was carried out from 2006 to 2014, in which the translocations ETV6/RUNX1, MLL/AF4, TCF3/PBX1, BCR/ABL1, as well as mutations in the PAX5 and FLT3 genes were evaluated through the use of different types of PCR. One hundred and thirty patients with a clinical diagnosis of acute lymphocytic leukemia were included in the study. Molecular alterations were identified in 56 patients (43.1%), in which we observed the presence of one or several alterations in conjunction in the same patient. The alterations identified were t(12; 21) (11.5%), t(4; 11) (8.5%), t(1; 19) (10%), t(9; 22) (20.8%), ITD-FLT3 (14.8%), P80S mutation (4.2%) and S77del (4.2%) in the PAX5 gene. The prevalence of BCR/ABL is one of the highest described so far in cases of ALL where most of the population is made up of pediatric patients. These results represent the first molecular study of ALL in Venezuela, laying the foundations for the diagnosis and monitoring of the disease in its population.
ABSTRACT
ABSTRACT Introduction: The ETV6-RUNX1 is a fusion gene associated with a good outcome in B-cell precursor lymphoblastic leukemia. Objective: This study aimed to re-evaluate the CD9 cellular expression by flow cytometry (FC) as a possible tool to predict the presence of ETV6-RUNX1. Method: Childhood B-cell precursor lymphoblastic leukemia cases were included (n = 186). The percentage of CD9-labeled cells and the median fluorescence intensity ratio were used for correlation with the molecular tests. Receiver Operating Characteristic curves were performed to determine the likelihood of the CD9 expression predicting ETV6-RUNX1. Results: The ETV6-RUNX1 was found in 44/186 (23.6%) cases. Data analysis revealed that the best cutoff for CD9 percentage was 64%, with an accuracy of 0.84, whereas the best cutoff for CD9 median fluorescence intensity ratio was 12.52, with an accuracy of 0.80. A strong association was observed between the level of CD9 expression and the presence of ETV6-RUNX1. Conclusion: These data confirm that the CD9 expression could be used for risk stratification in clinical practice.
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Biomarkers, Tumor , Gene Fusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Tetraspanin 29 , Flow Cytometry , ForecastingABSTRACT
Objective@#To investigate the clinical significance of monitoring ETV6-RUNX1 fusion gene in children with acute lymphoblastic leukemia (ALL) after allogeneic stem cell transplantation (allo-HSCT) .@*Methods@#Clinical data of 13 children received allo-HSCT in Peking University Institute of Hematology from May 2009 to March 2016 were retrospectively collected. The ETV6-RUNX1 gene was examined by real-time quantitative polymerase chain reaction (RQ-PCR) . The correlation between its expression level and the disease status was analyzed.@*Results@#Of 13 enrolled ALL cases, the ETV6-RUNX1 expression of 7 patients converted to positive after transplant at a median time of 137 days (range, 28-270 days) . The expression level of the first positive sample was 0.034% (range, 0.004%-0.061%) . The duration from ETV6-RUNX1 positive to hematological relapse was 196 days (range, 28-666 days) . Four patients experienced relapse at a median time of 294 days (range, 104-803 days) after allo-HSCT. The ETV6-RUNX1 expression converted to positive prior to MRD. Patients with positive ETV6-RUNX1 gene expression pre-transplantation would be more likely to relapse.@*Conclusion@#Monitoring ETV6-RUNX1 by RQ-PCR could be used to evaluate MRD status after allo-HSCT. Patients with positive ETV6-RUNX1 after transplant had a poor prognosis.
ABSTRACT
PURPOSE: ETV6/RUNX1 (+) acute lymphoblastic leukemia (ALL), which is the most common genetic subtype of pediatric ALL, has a favorable prognosis. In this study, we analyzed the outcome of ETV6/RUNX1 (+) ALL patients treated at our institution with the aim of identifying significant prognostic variables. MATERIALS AND METHODS: Sixty-three patients were diagnosed with ETV6/RUNX1 (+) ALL from 2005 to 2011. Prognostic variables studied included minimal residual disease (MRD) as detected by ETV6/RUNX1 (+) fusion, and the presence of additional cytogenetic abnormalities. RESULTS: The 5-year event-free survival was 84.1±4.6%, with 10 patients relapsing at a median of 28.3 months from diagnosis for a 5-year cumulative incidence of relapse of 15.9±4.6%. Multivariate analysis revealed that the presence MRD, as detected by real-time quantitative-polymerase chain reaction or fluorescence in situ hybridization for ETV6/RUNX1 fusion at end of remission induction, and the presence of additional structural abnormalities of 12p (translocations or inversions) negatively affected outcome. Despite treatment such as allogeneic hematopoietic cell transplantation, eight of the 10 relapsed patients died from disease progression for overall survival of 82.5±6.9%. CONCLUSION: ETV6/RUNX1 (+) ALL may be heterogeneous in terms of prognosis, and variables such as MRD at end ofremission induction or additional structural abnormalities of 12p could define a subset of patients who are likely to have poor outcome.
Subject(s)
Humans , Cell Transplantation , Chromosome Aberrations , Diagnosis , Disease Progression , Disease-Free Survival , Fluorescence , In Situ Hybridization , Incidence , Korea , Multivariate Analysis , Neoplasm, Residual , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Recurrence , Remission Induction , TransplantsABSTRACT
Objective To investigate the incidence of the ETV6/RUNX1 fusion gene among Chinese pediatric patients with B-ALL and its effect on the prognosis. Methods A total of 723 patients with B-ALL from January 1, 2007 to December 31, 2014 were enrolled in this study. All patients were detected ETV6/RUNX1 fusion gene by FISH. Clinical data and ETV6/RUNX1 were combined to analyze the clinical prognosis. Results Among the 723 patients, 151 were with ETV6/RUNX1 positive B-ALL, accounting for approximately 20.89%(151/723) of B-precursor cases;91 patients were with recurrence, including 10 patients with ETV6/RUNX1 positive B-ALL, and the recurrence rate of ETV6/RUNX1 positive B-ALL was 10.99%(10/91). Among 10 recurrent patients with ETV6/RUNX1 positive B-ALL, 9 patients relapsed more than 300 days later after diagnosis, while the recurrence times among the patients with ETV6/RUNX1 negative was very different. Although the recurrence times between the two groups showed no signiifcant difference (P?=?0.09), the recurrence times of ETV6/RUNX1 positive patients were mainly found at the end of clinical chemotherapy, while the recurrence time of ETV6/RUNX1 negative patients were mainly at maintaining chemotherapy period, there was a signiifcant difference between the distribution of recurrence time (P?