ABSTRACT
OBJECTIVE@#To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS.@*METHODS@#This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions.@*RESULTS@#Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0).@*CONCLUSION@#The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.
Subject(s)
Humans , Case-Control Studies , Genetic Predisposition to Disease , Interleukin-10/genetics , Polymorphism, Single Nucleotide , Spondylitis, Ankylosing/genetics , Transcriptional Elongation Factors/genetics , Nuclear Proteins/geneticsABSTRACT
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
Infant acute lymphoblastic leukemia B (B-ALL) accounts for 10% of childhood ALL. Eighty percent of infant B-ALL was caused byMLL gene rearrangement (MLL-r). The overall survival rate of ALL was less than 35% in infants with MLL-r. Among infant ALL with MLL-r, infants with positivefusion geneMLL-AF4 (MA4) formed by chromosome t (4;11) had even poor prognosis. Studies in monozygotic twins and archived blood spot at birth had veriifed that fusion gene MA4 originated from antenatal. Whole genome sequencing found that t (4;11) alone might be sufifcient to spawn leukemia. This paper is going to summarize the advances in biological characteristics such as clinical features, cellular origin, genomics and disease models of normalMLL gene and infant B-ALL withMA4.
ABSTRACT
Among several newly identified oncogenes, dek and af4 are attractive targets for researchers interested with leukemia. In this study quantitative Real-Time RT-PCR technique was used to define alterations in expression of dek and af4 genes associated with acute promyelocytic leukaemia (APL) t (15; 17). RNA samples obtained from bone marrow aspirates of fourteen APL patients, cDNA portions were labelled with Syber Green 1 dye and LightCycler analysis have been performed. Expression changes in patients were found not significant in comparison to healthy donors for af4 (P=0.192) and dek (P= 0.0895). We suggest that af4 gene may have a role in leukomogenesis restricted to lymphoblastic lineage; also further studies must carry on with a larger series of patients in order to understand the relationship between the dek gene and APL. Our study was the first attempt for analysing dek and af4 genes in APL t (15; 17) patients by quantitative Real-Time RT-PCR. This rapid and sensitive method could be used to screen these genes in different types of leukaemia.