Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia.

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status.

MiR-128-3p as blood based liquid biopsy biomarker in childhood acute lymphoblastic leukemia.

Background: Minimal residual disease (MRD) is one of the most valuable independent prognostic factors in acute lymphoblastic leukemia (ALL). Bone marrow (BM) aspiration, however, is an invasive process. Previous studies have shown that microRNAs (miR) and extracellular vesicle (EV)-related miRs show different expression profiles at the presence of malignant cells compared to healthy controls.

Co-Detection of VEGF-A and Its Regulator, microRNA-181a, May Indicate Central Nervous System Involvement in Pediatric Leukemia.

Central nervous system (CNS) involvement is a leading cause of therapy-refractory pediatric acute lymphoblastic leukemia (pALL), which is aggravated by underdiagnosing CNS disease with the currently used cell-based approach of cerebrospinal fluid (CSF) diagnostics. Our study focused on developing novel subcellular CNS leukemia indicators in the CSF and the bone marrow (BM) of patients with pALL. Serial liquid biopsy samples ( = 65) were analyzed by Elisas to measure the level of essential proteins associated with blast cell CNS trafficking, vascular endothelial growth factor A (VEGF-A) and integrin alpha 6 (ITGA6).

Melanoma susceptibility: an update on genetic and epigenetic findings.

Malignant melanoma is one of the most highly ranked cancers in terms of years of life lost. Hereditary melanoma with its increased familial susceptibility is thought to affect up to 12% of all melanoma patients. In the past, only a few high-penetrance genes associated with familial melanoma, such as and , have been clinically tested.

Pharmacogenetics of the Central Nervous System-Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia.

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events.

Two tagging single-nucleotide polymorphisms to capture HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype associated with asparaginase hypersensitivity.

Aims: Asparaginase (ASP) hypersensitivity is a well-known challenge in the treatment of lymphoblastic malignancies. In terms of cost considerations, the cheap native Escherichia coli ASP, the most immunogenic form of this medication, is used in the first line in middle-income countries. Previously, the role of the HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02 haplotype had been established to associate with E.

Investigation of circulating lncRNAs as potential biomarkers in chronic respiratory diseases.

Background: In the present study the blood expression level of inflammatory response and autoimmunity associated long non-coding RNAs (lncRNAs) were compared in patients with different chronic respiratory diseases and investigated whether they could be used as biomarkers in these diseases.

Methods: In the discovery cohort, the gene expression level of 84 lncRNAs were measured in the blood of 24 adult patients including healthy controls and patients with asthma and COPD. In the replication cohort the expression of 6 selected lncRNAs were measured in 163 subjects including healthy controls and adults with allergic rhinitis, asthma, COPD and children with asthma.

MicroRNA-181a as novel liquid biopsy marker of central nervous system involvement in pediatric acute lymphoblastic leukemia.

Background: Refractory central nervous system (CNS) involvement is among the major causes of therapy failure in childhood acute leukemia. Applying contemporary diagnostic methods, CNS disease is often underdiagnosed. To explore more sensitive and less invasive CNS status indicators, we examined microRNA (miR) expressions and extracellular vesicle (EV) characteristics.

Circulating microRNAs as minimal residual disease biomarkers in childhood acute lymphoblastic leukemia.

Background: Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other RNA classes.

Possible roles of genetic variations in chemotherapy related cardiotoxicity in pediatric acute lymphoblastic leukemia and osteosarcoma.

Background: The treatment of acute lymphoblastic leukemia (ALL) and osteosarcoma (OSC) is very effective: the vast majority of patients recover and survive for decades. However, they still need to face serious adverse effects of chemotherapy. One of these is cardiotoxicity which may lead to progressive heart failure in the long term.

HLA-DRB1*07:01-HLA-DQA1*02:01-HLA-DQB1*02:02 haplotype is associated with a high risk of asparaginase hypersensitivity in acute lymphoblastic leukemia.

Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to -derived asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian ALL population. Four-digit typing of and loci was performed in 359 pediatric ALL patients by using next-generation sequencing method.

Investigation of the Possible Role of the Hippo/YAP1 Pathway in Asthma and Allergy.

Purpose: Several lines of evidence indicate that the Hippo/Yes-associated protein 1 (YAP1) pathways might play a role in the pathogenesis of asthma. To investigate the possible role of the Hippo/YAP1 pathway in the pathogenesis of asthma or its phenotypes.

Methods: The levels of gene expressions of the members of the Hippo/YAP1 were compared.

[Extracellular vesicles and their role in hematological malignancies].

Extracellular vesicles are produced in all organisms. The most intensively investigated categories of extracellular vesicles include apoptotic bodies, microvesicles and exosomes. Among a very wide range of areas, their role has been confirmed in intercellular communication, immune response and angiogenesis (in both physiological and pathological conditions).

Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma.

Inter-individual differences in toxic symptoms and pharmacokinetics of high-dose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato- and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1, ABCC2, ABCC3, ABCC10, ABCG2, GGH, SLC19A1 and NR1I2 genes were analyzed in 59 patients with osteosarcoma.

Pharmacogenetics of anthracyclines.

Anthracyclines constitute a fundamental part of the chemotherapy regimens utilized to treat a number of different malignancies both in pediatric and adult patients. These drugs are one of the most efficacious anticancer agents ever invented. On the other hand, anthracyclines are cardiotoxic.

Impact of single nucleotide polymorphisms of cytarabine metabolic genes on drug toxicity in childhood acute lymphoblastic leukemia.

Background: Cytarabine (cytosine arabinoside, ara-C) is a chemotherapeutical agent used in the treatment of pediatric acute lymphoblastic leukemia (ALL). Adverse drug reactions, such as interpatient variability in sensitivity to ara-C, are considerable and may cause difficulties during chemotherapy. Single nucleotide polymorphisms (SNPs) can play a significant role in modifying nucleoside-drug pharmacokinetics and pharmacodynamics and thus the development of adverse effects.

Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis.

In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL) or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) methods.

Candidate gene association study in pediatric acute lymphoblastic leukemia evaluated by Bayesian network based Bayesian multilevel analysis of relevance.

Background: We carried out a candidate gene association study in pediatric acute lymphoblastic leukemia (ALL) to identify possible genetic risk factors in a Hungarian population.

Methods: The results were evaluated with traditional statistical methods and with our newly developed Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA) method. We collected genomic DNA and clinical data from 543 children, who underwent chemotherapy due to ALL, and 529 healthy controls.

Non-synonymous single nucleotide polymorphisms in genes for immunoregulatory galectins: association of galectin-8 (F19Y) occurrence with autoimmune diseases in a Caucasian population.

Background: Galectins are potent immune regulators, with galectin-8 acting as a pro-apoptotic effector on synovial fluid cells and thymocytes and stimulator on T-cells. To set a proof-of-principle example for risk assessment in autoimmunity, and for a mutation affecting physiological galectin sensor functions, a polymorphism in the coding region of the galectin-8 gene (rs2737713; F19Y) was studied for its association with two autoimmune disorders, i.e.

Asthma endophenotypes and polymorphisms in the histamine receptor HRH4 gene.

Background: Histamine as an inflammatory mediator plays an important role in chronic allergic and asthmatic conditions. However, the role of genetic polymorphisms of the histamine receptor HRH4 (histamine receptor H4) gene in asthma susceptibility and endophenotypes has not been studied yet. Our aim was to investigate the possible association between single nucleotide polymorphisms (SNPs) in the HRH4 gene and asthma or some endophenotypes of asthma.

Evaluation of a partial genome screening of two asthma susceptibility regions using bayesian network based bayesian multilevel analysis of relevance.

Genetic studies indicate high number of potential factors related to asthma. Based on earlier linkage analyses we selected the 11q13 and 14q22 asthma susceptibility regions, for which we designed a partial genome screening study using 145 SNPs in 1201 individuals (436 asthmatic children and 765 controls). The results were evaluated with traditional frequentist methods and we applied a new statistical method, called bayesian network based bayesian multilevel analysis of relevance (BN-BMLA).

Implication of BIRC5 in asthma pathogenesis.

In the last few years, it has been recognized that the unbalanced regulation of survival and apoptosis of bronchial inflammatory cells is a key component in the development of asthma. Baculoviral IAP repeat containing 5 (BIRC5) (also known as survivin) is an important anti-apoptotic protein that has been implicated in many cancer types, and recent studies provide evidence for its role in controlling inflammatory disorders as well. Our aim was to investigate at both genetic and transcriptional levels if BIRC5 has an impact on asthma development.

Relationship between air pollution, NFE2L2 gene polymorphisms and childhood asthma in a Hungarian population.

Air pollution and subsequent increased oxidative stress have long been recognized as contributing factors for asthma phenotypes. Individual susceptibility to oxidative stress is determined by genetic variations of the antioxidant defence system. In this study, we analysed the association between environmental nitrogen dioxide (NO(2)) exposure and single nucleotide polymorphisms (SNP) in NFE2L2 and KEAP1 genes and their common impact on asthma risk.