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It has been demonstrated previously that human leukocyte antigen class I (HLA-I) and class II (HLA-II) alleles may modulate JAK2 V617F and CALR mutation (CALRmut)-associated oncogenesis in myeloproliferative neoplasms (MPNs). However, the role of immunogenetic factors in MPNs remains underexplored. We aimed to investigate the potential involvement of HLA genes in CALRmut+ MPNs. High-resolution genotyping of HLA-I and -II loci was conducted in 42 CALRmut+ and 158 JAK2 V617F+ MPN patients and 1,083 healthy controls. A global analysis of the diversity of HLA-I genotypes revealed no significant differences between CALRmut+ patients and controls. However, one HLA-I allele (C*06:02) showed an inverse correlation with presence of CALR mutation. A meta-analysis across independent cohorts and healthy individuals from the 1000 Genomes Project confirmed an inverse correlation between the presentation capabilities of the HLA-I loci for JAK2 V617F and CALRmut-derived peptides in both patients and healthy individuals. scRNA-Seq analysis revealed low expression of TAP1 and CIITA genes in CALRmut+ hematopoietic stem and progenitor cells. In conclusion, the HLA-I genotype differentially restricts JAK2 V617F and CALRmut-driven oncogenesis potentially explaining the mutual exclusivity of the two mutations and differences in their presentation latency. These findings have practical implications for the development of neoantigen-based vaccines in MPNs. [ABSTRACT FROM AUTHOR]

For the management of information flow, the use of the functional modelling methodology is proposed, as part of the graph theory for describing the functioning of systems, such as public authorities as organizational-management structures. The methodology is based on concepts such as functional block and interface arc (flow). In organizational-management structures, one of the functional blocks is the manager, and the others are managed. Each of the blocks is a source of information and generates information flows, transferring information to a managed functional block or several ones. For the implementation and management of information exchange by the public authorities in crisis management, processing and protection of data flow, when working in a group environment, it is proposed to build an adequate communication and information system using the methodology of functional modelling. [ABSTRACT FROM AUTHOR]

For the management of information flow, the use of the functional modelling methodology is proposed, as part of the graph theory for describing the functioning of systems, such as public authorities as organizational-management structures. The methodology is based on concepts such as functional block and interface arc (flow). In organizational-management structures, one of the functional blocks is the manager, and the others are managed. Each of the blocks is a source of information and generates information flows, transferring information to a managed functional block or several ones. For the implementation and management of information exchange by the public authorities in crisis management, processing and protection of data flow, when working in a group environment, it is proposed to build an adequate communication and information system using the methodology of functional modelling. [ABSTRACT FROM AUTHOR]

The novel MICA*112:02 allele was detected by next generation sequencing. [ABSTRACT FROM AUTHOR]

Two novel MICB alleles with coding polymorphisms in exon 3 were detected by next generation sequencing. [ABSTRACT FROM AUTHOR]

This document is a letter published in the Annals of Hematology. The authors conducted a systematic analysis of copper, zinc, and selenium levels in patients with JAK2 V617F-positive myeloproliferative neoplasms (MPNs). They found that the presence of the JAK2 V617F mutation was associated with higher copper and zinc levels but lower selenium levels. Additionally, they observed that copper levels were higher in essential thrombocythemia (ET) and polycythemia vera (PV) patients, while zinc levels were higher in all three MPN entities. However, selenium levels were lower in all three entities compared to healthy controls. The authors suggest that these findings provide testable hypotheses for the role of copper, zinc, and selenium in MPNs and raise questions about the potential clinical justification for nutritional supplementation with these elements in JAK2 V617F-positive MPNs. [Extracted from the article]

This article starts an engagement on the aesthetics of experiments and offers an account for analysing how aesthetics features in the design, evaluation and reception of experiments. I identify two dimensions of aesthetic evaluation of experiments: design and significance. When it comes to design, a number of qualities, such as simplicity, economy and aptness, are analysed and illustrated with the famous Meselson-Stahl experiment. Beautiful experiments are also regarded to make significant discoveries, but I argue against a narrow construal of experimental aims. By drawing on the plurality of goals experimenters have and diversity of aesthetic responses, I argue that experiments are aesthetically appreciated both when they discover and when they produce disruptive results. [ABSTRACT FROM AUTHOR]

This study provides the first immunogenetic preliminary evidence that specific human leucocyte antigen (HLA) class I and class II alleles and haplotypes may be relevant for BRCA1 c.5263_5264insC driven oncogenesis. Observed HLA associations might have practical implications for establishment of predictive markers for the response to immunotherapies in malignancies driven by this germ‐line mutation. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is the major pathological subtype of laryngeal cancer. It has been shown that alterations of the expression of non-classical human leukocyte antigens (HLA) and the chain-related MIC molecules by malignant cells can lead to escape from the immune system control and certain allele variants may participate in immune editing and therefore be associated with modulation of cancer risk. The aim of the present study was to investigate the role of non-classical HLA class Ib and chain-related MIC polymorphisms, determined at the allelic level by next-generation sequencing (NGS), in patients from the Bulgarian population, diagnosed with LSCC. Materials and methods: In the present study DNA samples from 48 patients with LSCC were used. Data was compared to 63 healthy controls analysed in previous studies. HLA genotyping was performed by using the AlloSeq Tx17 early pooling protocol and the library preparation AlloSeq Tx17 kit (CareDx). Sequencing was performed on MiniSeq sequencing platform (Illumina) and HLA genotypes were assigned with the AlloSeq Assign analysis software v1.0.3 (CareDx) and the IPD-IMGT/HLA database 3.45.1.2. Results: The HLA disease association tests revealed a statistically significant predisposing association of HLA-F*01:01:02 (Pc = 0.0103, OR = 24.0194) with LSCC, while HLA-F*01:01:01 (Pc = 8.21e-04, OR = 0.0485) has a possible protective association. Additionally we observed several haplotypes with statistically significant protective and predisposing associations. The strongest association was observed for F*01:01:01-H*01:01:01 (P = 0.0054, haplotype score=-2.7801). Conclusion: Our preliminary study suggests the involvement of HLA class Ib in cancer development and the possible role of the shown alleles as biomarkers of LSCC. [ABSTRACT FROM AUTHOR]

JAK2 V617F‐driven myeloproliferative neoplasms (MPNs) can escape immune surveillance through PD‐L1 up‐regulation and HLA class I pathway down‐regulation. To complement these data we assessed the role of major histocompatibility complex class I—related genes (MICA and MICB) in JAK2 V617F+ MPNs. Using high resolution genotyping we identified two protective alleles, MICA*008:01 and MICA*016. MPN patients had significantly higher levels of soluble sMICA molecules. Peripheral blood JAK2 V617F+ granulocytes had higher surface expression of MICB but did not differ in the amount of MICA and MICB transcripts from normal granulocytes. MICA and MICB genes were significantly down‐regulated in JAK2 V617F+ CD34+ cells from primary myelofibrosis patients in comparison to normal CD34+ hematopoietic stem cells. These data suggest minor but significant role of MICA and MICB genes in the pathogenesis of MPNs. It is also possible that MICA targeting approaches could be of clinical benefit for some of those patients. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is an autoimmune bullous dermatosis with uneven geographic distribution and higher incidence in certain populations. In previous studies, a relatively high incidence of PV was reported in Bulgaria (0.47/100,000/year) comparable to that in other countries. The genetic background was considered responsible for the disease susceptibility, and multiple reports have proven PV to be an HLA-associated condition. The aim of our study was to analyze the role of genetic factors in the development of PV in Bulgaria. HLA genotyping was performed in 56 PV patients, ethnic Bulgarians whose diagnosis was confirmed based on clinical, histological, and immunofluorescent findings. The control group consisted of 204 healthy individuals from the Bulgarian population without evidence for HLA- associated autoimmune diseases. HLA-A,-B,-DRB1,-DQB1 analysis was performed by PCR-SSP. Our results revealed predisposing associations with DRB1*14, DRB1*04:02, and B*38, B*55, while allele DRB1*03:01 and the corresponding haplotypes were significantly decreased in the PV patients. The predisposing role of these alleles has been observed in other populations. All reported predisposing DRB1 alleles have the same amino acids at key positions of the beta chain of the HLA molecules, 26 (Phe), 67 (Leu or Ileu), 70 and 71 (hydrophobic AA: Gln, Arg, Asp, or Glu), and 86 (Val), which is important for the selective presentation of desmoglein 3 peptides. Additionally, specific alleles HLA-A*01 and DRB1*11 were identified with decreased frequencies in the patients' group, the last one being a common protective allele for autoimmune diseases in the Bulgarian population. The elucidation of the role of genetic factors for the development of pemphigus will help explain its higher incidence and clinical variability in certain populations. [ABSTRACT FROM AUTHOR]

Polymorphisms in the genes of drug-metabolizing enzymes have the potential to contribute to inter-individual differences in drug pharmacokinetics and toxicity. A custom next-generation sequencing (NGS) panel was used in 71 kidney transplanted patients to study the polymorphisms of 11 genes relevant to the metabolism of immunosuppressive drugs. Cyclosporine A and tacrolimus concentrations were determined by a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. More than 1000 polymorphisms were found in the studied 11 genes, and 45% of them were different non-synonymous variants. Eleven missense mutations were observed in the CYP3A7 gene, resulting in increased metabolism of tacrolimus at day 21 post-transplantation (6.7 µg/L vs. 10.3 µg/L; p = 0.048). Two alleles encoding a cytochrome P450 2D6 enzyme with impaired function—CYP2D6*4 (non-functional) and CYP2D6*10 (decreased function), were found in the studied group and both of them were associated with higher levels of tacrolimus at day 14 (10.1 µg/L; p = 0.021 and 9.7 µg/L; p = 0.036, vs. 7.7 µg/L respectively). Altered function of ABC transporters C3 and C2 was also associated with increased TAC concentration. ABCC3 significantly influenced TAC metabolism by itself, but polymorphisms affecting both ABCC3 and ABCC2 resulted in higher changes: 13.6 µg/L vs. 7.9 µg/L, day 14 (p = 0.003) and 20 µg/L versus 9.3 µg/L, day 21 (p = 0.019). All associations were also checked for variants affecting the activity of CYP3A4 and CYP3A5. Despite its small size, the study points out that the pharmacogenetics of calcineurin inhibitors may also be influenced by other genes besides CYP3A4 and CYP3A5. [ABSTRACT FROM AUTHOR]

Background: Oral Squamous Cell Carcinoma (OSCC) is a malignancy characterized by an aggressive tumor growth and significant mortality. Clarifying mechanisms responsible for immunomodulation are among the main challenges for the development of personalized approaches for the management of patients with Oral Squamous Cell Carcinoma. The aim of the present study was to analyze the relevance of MICA and MICB to Oral Squamous Cell Carcinoma pathogenesis focusing on allele polymorphisms and the levels of soluble MICA and MICB molecules.Materials and Methods: 73 patients diagnosed with Oral Squamous Cell Carcinoma and 149 healthy controls from the Bulgarian population were included in the study. MICA and MICB polymorphism was analyzed at high-resolution level using Next-Generation Sequencing. Serum levels of soluble MICA and MICB molecules were measured by ELISA.Results: Our results show significant protective association with MICB*002:01, while relatively rare alleles MICB*018, *019, and *020 were observed with statistically significant increased frequency in Oral Squamous Cell Carcinoma patients compared to controls. Additionally, a predisposing association was observed for MICA*008:01-MICB*019 haplotype. A correlation analysis between functionally relevant MICA polymorphisms and sMICA showed that homozygosity for MICA-A5.1 or 129Val in OSCC patients was associated with significantly higher serum levels of sMICA.Conclusion: This is the first study showing significant associations between MICB alleles and Oral Squamous Cell Carcinoma and suggesting the possible role of MICB in immunosurveillance in Oral Squamous Cell Carcinoma development. Observed correlations between the levels of soluble MICA molecules and functionally relevant polymorphisms might represent a further step toward a better understanding of molecular mechanisms of Oral Squamous Cell Carcinoma and developing strategies for therapeutic targeting harnessing effective immunosurveillance. [ABSTRACT FROM AUTHOR]

Newton's laws of motion or Einstein's light postulate and equivalence principle are examples of such fundamental principles that Newtonian mechanics and the special and general theory of relativity, respectively, are built upon. With the rise of behavioural economics as a serious rival to neoclassical economics and to alternative schools such as Austrian economics, the debate about the nature, status and function of first principles in economics has become prevalent again. As such, while Mill takes those principles to be infallible because testing them is impossible for epistemic reasons, Robbins views those principles - particularly the principle of constrained optimization - as a priori and infallible; they cannot be falsified but only wrongly applied. With Becker and Stigler, the key first principles of economics - the principle of constrained optimization and the principle that preferences are stable - are ultimately justified by their pragmatic success in explanations and predictions and as such are supportable by empirical evidence; they are indubitable but fallible. [Extracted from the article]

The implementation of the immune checkpoint blockade as a therapeutic option in contemporary oncology is one of the significant immunological achievements in the last century. Constantly accumulating evidence suggests that the response to immune checkpoint inhibitors (ICIs) is not universal. Therefore, it is critical to identify determinants for response, resistance and adverse effects of immune checkpoint therapy that could be developed as prognostic and predictive markers. Recent large scale analyses of cancer genome data revealed the key role of HLA class I and class II molecules in cancer immunoediting, and it appears that HLA diversity can predict response to ICIs. In the present review, we summarize the emerging data on the role of HLA germline variations as a marker for response to ICIs. [ABSTRACT FROM AUTHOR]

This article explores the aesthetic dimensions of scientific experimentation, addressing specifically how aesthetic features enter the construction, evaluation and reception of an experiment. I highlight the relationship between experiments and artistic acts in the early years of the Royal Society where experiments do not serve only epistemic aims but also aim to generate feelings of awe and pleasure. I turn to analysing which aspects of experiments are appreciated aesthetically, identifying several contenders, from the ability of an experiment to uncover nature's beauty, to encapsulating original designs and human creativity. Following this analysis, I focus on the notion of beauty: what makes an experiment beautiful? Several common qualities are explored, from the simplicity and economy of the experiment, to the significance of the experimental results. [ABSTRACT FROM AUTHOR]

Jean Perrin is considered to have given conclusive evidence for the existence of atoms and molecules and to have ended the long debate regarding the reality of atoms. Both Hudson and Coko want to understand the significance of the multiple determinations of I N i in Perrin's argument, and the importance placed on the no-coincidence argument and on analogical reasoning. Both Coko and Hudson, for instance, take it that longtime anti-atomists, such as Henri Poincaré and Wilhelm Ostwald, converted to atomism after Perrin's work. They emphasize Poincaré's claim that Perrin had made atoms observable, and take Ostwald to admit the truth of the atomic hypothesis. [Extracted from the article]

The paper reports on a successful observation of high resolution Fourier transform spectra of LiCa. The fine structure of the ground state was observed and attributed to effective spin-rotation interaction. The experimental observations are described by two models using potential energy curves. One of them takes into account the fine structure splitting by means of effective constants, the other by means of a R dependent function γ(R), built in the radial Schrödinger equation. Ab initio calculations were performed for γ(R) which comes close to the experimental function. [ABSTRACT FROM AUTHOR]

We report on the first experimental observation of the ground electronic state of the LiRb molecule at high resolution. A large body of experimental data was collected which led to an accurate potential energy curve for this state. Transitions to the lowest triplet state were also observed, but these data are rather fragmentary and allow only a first attempt for the description of this state. Both potentials were used for evaluating published Feshbach resonances of this molecule. We compare the results of this study with those of the related LiK and LiCs molecules. [ABSTRACT FROM AUTHOR]

We provide evidence for a linear correlation between the frequency of clonal haematopoiesis and COVID‐19 mortality rate. We discuss the mechanistic explanations for this association mediated by a pathological inflammatory response. Our hypothesis can be tested in COVID‐19‐infected patients and eventually lead to new approaches to risk stratification and therapy. [ABSTRACT FROM AUTHOR]

The possibility to utilize waste aluminum slag and refractory clay as raw materials for production of ceramic industry is studied. The effect of the amount of waste aluminium slag on the physicochemical and mechanical properties of the samples obtained at different temperatures is followed. A maximum density of 2,10.103 kg/m3 and a bending strength of 23,2 ÌÐà are achieved. The materials synthesized can be classified as high aliminium oxide refractory materials and can successfully be used in practice. [ABSTRACT FROM AUTHOR]

The article discusses research which analyzed the National Cancer Institute's (NCI) Surveillance, Epidemiology and End Results (SEER) program which released the April 2017 standardized incidence ratio (SIR) of second solid cancers in mastocytosis patients. The article explains the SIR assessment of the rate of development of second malignancies. Also mentioned is the statistically increased risk of second cancer driven by the presence of hematologic malignancies.

The presented study revealed that there were changes in the phenolic compounds profi le of extract of wild thyme (Thymus serpyllum L.) after γ-irradiation at the dose of 5 kGy. Ethanolic extracts of irradiated and non-irradiated herb were prepared and their compounds were analyzed by RP- -HPLC-DAD technique. Between thirty two detected constituents, twelve phenolic compounds classifi ed as hydroxybenzoic and hydroxycinnamic acids derivatives, fl avones and fl avanones were identifi ed. Among them, caffeic acid derivatives and fl avones predominated with the highest content of rosmarinic acid and luteolin-7-O-glucoside, respectively. Additionally, thymol was recognized in the analyzed extracts. γ-Irradiation slightly affected the quantitative profi le of phenolic compounds of a wild thyme ethanolic extract. Only four constituents differed signifi cantly (P<0.05) in terms of their content in the irradiated and non-irradiated samples. The content of phenolic acids (p-coumaric and caffeic acids) decreased and that of fl avonoid aglycons (luteolin and eriodictyol) increased after the γ-ray treatment. [ABSTRACT FROM AUTHOR]

Scientists often use aesthetic values in the evaluation and choice of theories. Aesthetic values are not only regarded as leading to practically more useful theories but are often taken to stand in a special epistemic relation to the truth of a theory such that the aesthetic merit of a theory is evidence of its truth. This paper explores what aesthetic considerations influence scientists' reasoning, how such aesthetic values relate to the utility of a scientific theory, and how one can justify the epistemic role for such values. The paper examines ways in which the link between beauty and truth can be defended, the challenges facing such accounts, and explores alternative epistemic roles for aesthetic values in scientific practice. [ABSTRACT FROM AUTHOR]

This paper offers a systematic analysis of Poincaré's understanding of beauty in science. In particular, the paper examines the epistemic significance Poincaré attributes to aesthetic judgement by reconstructing and analysing his arguments on simplicity and unity in science. I offer a consistent reconstruction of Poincaré's account and show that for Poincaré simplicity and unity are regulative principles, linked to the aim of science-that of achieving understanding of how phenomena relate. I show how Poincaré's account of beauty in science can be incorporated within his wider philosophy of science. [ABSTRACT FROM AUTHOR]

The role intellectual virtues play in scientific inquiry has raised significant discussions in the recent literature. A number of authors have recently explored the link between virtue epistemology and philosophy of science with the aim to show whether epistemic virtues can contribute to the resolution of the problem of theory choice. This paper analyses how intellectual virtues can be beneficial for successful resolution of theory choice. We explore the role of virtues as well as vices in scientific inquiry and their beneficial effects in the context of theory choice. We argue that vices can play a role in widening the set of potential candidate theories and support our claim with historical examples and normative arguments from formal social epistemology. We argue that even though virtues appear to be neither necessary nor sufficient for scientific success, they have a positive effect because they accelerate successful convergence amongst scientists in theory choice situations. [ABSTRACT FROM AUTHOR]

Objectives: In the last decade the identification of germline mutations in several genes such as EPOR, VHL, EGLN1, and EPAS1, helped the definition of several different subtypes of familial (congenital) erythrocytosis. Being rare disorders these entities often remain unrecognized or misdiagnosed, which necessitates the extensive reporting of newly identified cases. Methods: We applied a genetic approach including whole exome sequencing and Sanger sequencing for the identification of the causative germline mutation in a Bulgarian family with congential erythrocytosis. Results: We identified EPAS1 (HIF2A) p. M535T heterozygous mutation carried by four members of the family over three generations. We provide also an extensive description of the clinical features of the affected family members. Discussion: EPAS1 p.M535T appears to be found in different populations as a causative variation in familial erythrocytosis. Our findings support the notion that the affected patients present with variable clinical features and disease course. Furthermore, close clinical follow-up with phlebotomies on demand and regular intake of low doses of anticoagulants seem to prevent from serious complications such as thrombembolic events and pulmonary hypertension. Conclusion: This is the first description of an entire family with EPAS1 p. M535T mutation expanding our knowledge about the clinical features of the disease. [ABSTRACT FROM AUTHOR]

Many studies have described the role of killer immunoglobulin-like receptors (KIRs) and their cognate human leukocyte antigen (HLA) class I ligands in the immune protection against melanoma, but the effect of these markers on intra-individual variations in tumor development and progression has remained less clear. We performed KIR, HLA, and KIR/ligand analysis in 283 patients with malignant melanoma in order to evaluate their integrated influence on disease stage and progression. The patients were grouped according to AJCC staging, histological type of the primary tumor, progression, and survival rate. Analysis of HLA class I alleles revealed positive association of HLA-C*14 (Pc = 0.026, OR = 5.99) and negative association of HLA-C*02 (Pc = 0.026, OR = 0.43) with the disease. Decreased frequency of KIR2DS5 was observed in patients with rapid progression, as compared to those with slow progression. KIR BB genotype was prevalent in patients with metastasis ( p = 0.004, OR = 0.025). KIR AA genotype was nearly twice as frequent in rapidly progressive cases, but without statistical relevance ( p = 0.055, OR = 2.6). Significantly increased frequency of KIR2DL2 in the presence of C1 ligand (strong inhibition) was found in patients with AJCC III and IV, as compared to individuals with AJCC I stage ( p = 0.045, OR = 1.93). In summary, our data imply that KIR/ligand gene content in patients could modulate the disease course towards unfavorable tumor behavior. [ABSTRACT FROM AUTHOR]

Background and Objective: In the last decade, a number of genes have been reported to be recurrently associated with myeloid malignancies. While some mutations are easily detectable by conventional molecular genetics methods, other mutations are more difficult to screen because of lower frequency and being scattered along large genomic ranges. However, newly developed approaches for next-generation sequencing provide an affordable solution for targeted multiplex resequencing of up to several hundreds of amplicons. Here, we aimed to develop and validate a novel custom panel for targeted resequencing of myeloid malignancy samples using the Ion PGM™ System (Ion Torrent, Paisley, UK). Methods: We designed a pool of 424 primers for the amplification of 212 amplicons covering 99.46 % of the exonic regions of nine human genes as follows: ASXL1, EZH2, CALR, RUNX1, SETBP1, SF3B1, SRSF2, TET2, and U2AF1. Initial testing of the panel performance was performed on an Ion PGM™ machine using PGM™ 316 v2 chips on 16 DNA samples from patients with myeloid malignancies. Sequence alignment, variant calling, and annotation were performed using Ion Reporter software. Results: We identified a total of 14 nonsynonymous somatic coding variants in seven samples affecting six of the genes in the panel ( ASXL1, CALR, RUNX1, SRSF2, TET2, and U2AF1). Notably, three of the identified mutations were not present in the Cosmic v.67 release. Conclusion: This proof-of-concept study confirms the feasibility of Ion Torrent systems for resequencing of clinically relevant mutations in myeloid malignancies. It can be particularly useful in cases without the most frequent clonal markers. [ABSTRACT FROM AUTHOR]

Using a method for constructing self-dual codes having an automorphism of odd prime order, we classify up to equivalence all binary self-dual codes with an automorphism of order 11 with 6 cycles and minimum distance 12. This classification gives new [72, 36, 12] codes with weight enumerator that was previously not obtained as well as many [66, 33, 12], [68, 34, 12], and [70, 35, 12] codes with new values of the parameters in their respective weight enumerators. [ABSTRACT FROM PUBLISHER]

Mutations in the human DNA methyl transferase 3A (DNMT3A) gene are recurrently identified in several hematologic malignancies such as Philadelphia chromosome-negative myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), MPN/MDS overlap syndromes and acute myeloid leukemia (AML). They have been shown to confer worse prognosis in some of these entities. Notably, about 2/3 of these mutations are missense mutations in codon R882 of the gene. We aimed at the development and validation of a novel easily applicable in routine practice method for quantitative detection of the DNMT3A p.R882C/H/R/S mutations bead-based suspension assay. Initial testing on plasmid constructs showed excellent performance of BNA(NC)-modified probes with an optimal hybridization temperature of 66°C. The method appeared to be quantitative and showed sensitivity of 2.5% for different mutant alleles, making it significantly superior to direct sequencing. The assay was further validated on plasmid standards at different ratios between wild type and mutant alleles and on clinical samples from 120 patients with known or suspected myeloid malignancies. This is the first report on the quantitative detection of DNMT3A R882 mutations using bead-based suspension assay with BNA(NC)-modified probes. Our data showed that it could be successfully implemented in the diagnostic work-up for patients with myeloid malignancies, as it is rapid, easy and reliable in terms of specificity and sensitivity. [ABSTRACT FROM AUTHOR]

MicroRNAs are a class of small noncoding RNAs playing a crucial role in physiological and pathological conditions, including acute myeloid leukemia. We aimed at examining whether in clinical settings the identification of patient-specific leukemia-associated profiles (LAMPs) of overexpressed microRNAs could be used for minimal residual disease (MRD) detection. Patients with identified LAMPs at diagnosis were further tested for the presence of LAMP after induction therapy. Those with identifiable MRD defined by LAMP expression after induction showed a trend toward a shorter overall survival. Larger studies are needed to confirm the utility of patient-specific LAMPs for MRD follow-up. [ABSTRACT FROM AUTHOR]