scholarly journals Prognosis in patients with MDS or AML and bone marrow blasts between 10% and 30% is not associated with blast counts but depends on cytogenetic and molecular genetic characteristics

Leukemia ◽  
2011 ◽  
Vol 25 (8) ◽  
pp. 1361-1364 ◽  
Author(s):  
U Bacher ◽  
W Kern ◽  
T Alpermann ◽  
S Schnittger ◽  
A Kohlmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Molecular Genetic ◽  
Genetic Characteristics ◽  
Bone Marrow Blasts

scholarly journals Mantle Zone Cell Lymphomas. New Opportunities for Diagnosis and Treatment (Epidemiological Research)

2020 ◽  
Vol 9 (4) ◽  
pp. 261-265
Author(s):  
E. I. Kankumasheva ◽  
Ch. Kh. Valiakhmetova
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Molecular Genetic ◽  
Epidemiological Data ◽  
Patient Specific ◽  
High Dose ◽  
Rare Type ◽  
Genetic Characteristics ◽  
Mantle Cell

Introduction. Mantle cell lymphoma is a rare type of B-cell non-Hodgkin lymphoma. According to statistics the incidence of this disorder amounts to 2-3 per 100,000 people; this is about 6% of all non-Hodgkin lymphomas. It has been established that various molecular genetic characteristics of mantle cell lymphoma patients may present opportunities for a patient-specific approach to the disease prognosis and treatment strategy.Materials and methods. The paper presents a retrospective analysis of 45 mantle cell lymphoma patients treated at the GAUZ RKOD of the Ministry of Healthcare from 2015 until now. The data used in the analysis included clinical examination, lab panels, PET CT, tumour and bone marrow biopsy specimen cytology, histology and immunohistochemistry. We analysed the epidemiological data, the patients’ clinical presentation characteristics, treatment approaches, immediate and long-term outcomes.Results and discussion. We have established that the pathological process most frequently involves bone marrow (44%) and spleen (41%). The MIPI scores distribution was as follows: high in 14 (30%), medium in 20 (45%), low in 11 (41%). Ki67 was recorded at under 30% in four cases, in others it amounted to over 30%. In 2015–2017 patients were treated with the R-CHOP protocol with the following support with rituximab. PFS averaged at 20 months, 8 (17%) of patients remain in lasting remission (since 2015). In 2017 the R-BAC (high dose cytarabine for SCT candidates) and R-B (for the elderly and comorbid patients) became protocols of first line. Since 2018 eight patients have undergone auto-SCT (at the first late recurrence) as a treatment consolidation stage. As of now 13 patients have been examined in federal centres for del17p and the TP53 mutation.Conclusion. We have demonstrated the need for and the option of treatment depending on the results of molecular genetic testing of mantle cell lymphomas.

Clinical application of polymorphic variants of the genes ESR1 and CYP2D6*4 in patients with breast and endometrial cancer

2017 ◽  
pp. 132-138
Author(s):  
O.V. Paliychuk ◽  
◽  
L.Z. Polishchuk ◽  
Z.I. Rossokha ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Hormone Therapy ◽  
Molecular Genetic ◽  
Cancer Syndrome ◽  
Genetic Characteristics ◽  
Multiple Tumors ◽  
Receptor Status ◽  
Genetic Examination ◽  
The Impact

The objective: determining gene polymorphism features ERS1, CYP2D6 in patients with breast cancer (RHZ) and endometrial cancer (EC) and the impact assessment studied genetic characteristics compared to receptor status (immunohistochemical determination of expression levels of ER, PR) tumors and the results of the treatment. Patients and methods. article presents the results of complex clinical, morphological, clinical-genealogical, and molecular-genetic examination of 28 females: 19 patients with breast cancer (BC), 9 patients with endometrial cancer (EC), including 5 patients with primary-multiple tumors (PMT) with and without tumor pathology aggregation in families. Results. The It was determined that in patients’ families malignant tumors of breast, uterine body and/or ovaries prevail that corresponds to Lynch type II syndrome (family cancer syndrome). Molecular-genetic examination of genomic DNA of peripheral blood and histological sections for the presence of SNPs of ESR and CYP2D6*4 genes comparing with the results of immunohistochemical study of tumors for receptors ER and PR status have not found associations between these characteristics; although among EC patients the occurrence of genotypes 397ТТ and 351АА was significantly higher comparing with BC patients (55.55% and 10.5% for genotype 397ТТ,and 15.8% for genotype 351АА, respectively). At the same time the patients with BC and primary-multiple tumors (PMT) of female reproductive system organs (FRSO) that carried mutations in BRCA1 in all the cases demonstrated positive ER and PR receptor status and adverse combinations of polymorphous variants of the genes ESR1 (397СС, 397ТС) and CYP2D6*4 (1846G, 1846GA), suggesting combined effect of these factors on the development of malignant neoplasias of FRSO in families with positive family cancer history. In BC patients, receiving standard hormone therapy with tamoxifen, those, who had genotype 1846GG of the gene CYP2D6*4, in 3 patients (15.8%) of 19 (100%) patients disease recurrence was diagnosed. Conclusion. The obtained results allow clinical use of the assessment of polymorphism frequency of the genes ESR1 and CYP2D6*4 for selection of individual hormone therapy regimens schemes for BC patients, to increase efficacy of dispensary observation after finishing of special therapy for such patients, and also personalization of complex and combined treatment regimens. Key words: breast cancer, endometrial cancer, family cancer syndrome, single nucleotide polymorphisms (SNPs) of the genes ESR1, CYP2D6*4.

Thickness of endometrium: predictor of the effectiveness of IVF/ICSI programs (literature review)

GYNECOLOGY ◽  
2018 ◽  
Vol 20 (1) ◽  
pp. 113-116
Author(s):  
L A Bagdasaryan ◽  
I E Korneyeva
Keyword(s):  
Assisted Reproductive Technologies ◽  
Endometrial Thickness ◽  
Molecular Genetic ◽  
Uterine Cavity ◽  
Reproductive Technologies ◽  
Genetic Characteristics ◽  
Vitro Fertilization ◽  
Need To Evaluate ◽  
The Relationship

The aim of the study is to systematically analyze the data available in the modern literature on the relationship between endometrial thickness and the frequency of pregnancy in the program of assisted reproductive technologies (ART). Materials and methods. The review includes data from foreign and domestic articles found in PubMed on this topic. Results. The article presents data on the relationship between the thickness of the endometrium and the frequency of pregnancy in ART programs. The greatest number of studies is devoted to the evaluation of the relationship between the thickness of the endometrium and the frequency of pregnancy on the day of the ovulation trigger. Data are presented on the existence of a correlation between the thickness of the endometrium measured on the day of the ovulation trigger and the frequency of clinical pregnancy, as well as data on the need to evaluate the structure of the endometrium and the state of subendometric blood flow. The importance of multilayered (three-layered) endometrium as a prognostic marker of success in in vitro fertilization/intracytoplasmic sperm injection programs in the ovum is emphasized. The conclusion. The thickness of the endometrium can not be used as an argument for canceling the cycle or abolishing embryo transfer to the uterine cavity. Further studies in this direction are needed with a study of the morphological and molecular genetic characteristics of the endometrium, which in the future will allow us to evaluate the relationship between the thickness of the endometrium and the probability of pregnancy.

scholarly journals Influence of height on endothelial maintenance activity: a narrative review

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Yuji Shimizu ◽  
Takahiro Maeda
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Stem Cells ◽  
Bone Marrow ◽  
Hematopoietic Stem Cells ◽  
Inverse Association ◽  
Hematopoietic Stem ◽  
Genetic Characteristics ◽  
Maintenance Activity ◽  
Marrow Activity

AbstractRecent studies have revealed an inverse association between height and cardiovascular disease. However, the background mechanism of this association has not yet been clarified. Height has also been reported to be positively associated with cancer. Therefore, well-known cardiovascular risk factors, such as increased oxidative stress and chronic inflammation, are not the best explanations for this inverse association because these risk factors are also related to cancer. However, impaired blood flow is the main pathological problem in cardiovascular disease, while glowing feeding vessels (angiogenesis) are the main characteristic of cancer pathologies. Therefore, endothelial maintenance activity, especially for the productivity of hematopoietic stem cells such as CD34-positive cells, could be associated with the height of an individual because this cell contributes not only to the progression of atherosclerosis but also to the development of angiogenesis. In addition, recent studies have also revealed a close connection between bone marrow activity and endothelial maintenance; bone marrow-derived hematopoietic stem cells contribute towards endothelial maintenance. Since the absolute volume of bone marrow is positively associated with height, height could influence endothelial maintenance activity. Based on these hypotheses, we performed several studies. The aim of this review is not only to discuss the association between height and bone marrow activity, but also to describe the potential mechanism underlying endothelial maintenance. In addition, this review also aims to explain some of the reasons that implicate hypertension as a major risk factor for stroke among the Japanese population. The review also aims to clarify the anthropological reasons behind the high risk of atherosclerosis progression in Japanese individuals with acquired genetic characteristics.

MOLECULAR GENETIC CHARACTERISTICS OF COMPONENTS OF THE COMPLEMENT SYSTEM IN SEVERE ACNE

2021 ◽  
Vol 100 (2) ◽  
pp. 40-48
Author(s):  
A.G. Rumyantsev ◽  
◽  
A.G. Rumyantsev ◽  
O.M. Demina ◽  
◽  
...  
Keyword(s):  
Nucleotide Sequence ◽  
Complement System ◽  
Molecular Genetic ◽  
Factor H ◽  
Host Cells ◽  
Pathophysiological Mechanism ◽  
Genetic Characteristics ◽  
Severe Acne ◽  
C3 Gene ◽  
The Complement System

It has been shown that the inflammatory response in acne develops at the early subclinical stages of the disease, sometimes before the formation of comedones. It is known that an important component of the innate immune system is the complement system, which includes more than 60 components, including 9 basic proteins (C1-C9), a variety of activation products (C3a, C3b, iC3b, C3d and C3dg), regulatory and inhibitory molecules [factor H, fH-like protein 1 (FHL1), CR1 (CD35), C4b-binding protein (C4BP), C1inh and vitronectin], proteases and secreted enzymes (factor B, factor D, C3bBb and C4bC2b), as well as receptors for effector molecules [C3aR, C5aR, C5L2 and C1q receptor (C1qR)]. The compliment is the central part of innate immunity, which is the first line of protection against alien and altered host cells. The objectives of this study were to determine and analyze the variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9 in patients with severe acne. Materials and methods of research: To achieve the target a prospective open non-randomized one-center study was carried out in 2017–2020. Under our supervision in the clinical setting at the Department of Skin Diseases and Cosmetology of the Pirogov Russian National Research Medical University, there were 50 patients in the main group and 20 participants in the comparison group (70 people in total) (42/60% men and 28/40% women) aged 15 to 46 years (median – 22,1 years). Molecular genetic diagnostics was performed in all 70 patients of the main and control groups by the method of high-throughput DNA sequencing – next-generation sequencing (NGS). Results: when analyzing the nucleotide sequence variants of the complement system genes identified in our study, it is shown that the severe form of acne probably has an association (4 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 3 SNPs of the C3 gene, 2 SNPs of the C9 gene, 1 SNPs of the C7 gene, 1 SNPs of the C6 gene, 1 SNPs of the C2 gene, 2 SNPs of the C5 gene, 2 SNPs of the C8G gene), 13 SNPs of the complement system genes in introns (1 SNPs of the C8A gene, 1 SNPs of the C8B gene, 2 SNPs of the C1S gene, 1 SNPs of the C3 gene, 1 SNPs of the C7 gene, 2 SNPs of the C6 gene, 4 SNPs of the C5 gene, 1 SNPs of C8G gene), 6 SNPs of the complement system genes (2 SNPs of the C8B gene: one SNPs each in the 3'UTR and 5'UTR zones; 3 SNPs of the C3 gene in the 5'UTR zone, 1 SNPs of the C7 gene in the 3'UTR zone). Two mutations of the frame shift of the C2 gene (frameshift deletion) and the C9 gene (rs748464075, frameshift insertion) seem to have a protective effect in the development of acne. Conclusion: the obtained variants of the nucleotide sequence of the genes of the complement system C1QA, C1S, C2, C3, C5, C6, C7, C8A, C8B, C8G, C9, apparently, are associated with the formation of severe acne and cause an imbalance of the components of the complement system. It can cause a defect in chemotactic and phagocytic reactions, and as a result a disturbance of the regulation of the inflammatory reaction with chronization of the skin process occures. Thus, results of studies carried out, revealed – for the first time – polymorphic loci of genes of components of the complement system, the imbalance of which is the pathophysiological mechanism of acne.

Clinical and genetic characteristics of rare pathogenic variants of the CFTR gene in Russian patients with cystic fibrosis

2021 ◽  
Vol 31 (2) ◽  
pp. 148-158
Author(s):  
A. Yu. Voronkova ◽  
Yu. L. Melyanovskaya ◽  
N. V. Petrova ◽  
T. A. Adyan ◽  
E. K. Zhekaite ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Genetic Variants ◽  
Pancreatic Insufficiency ◽  
Protein Energy Malnutrition ◽  
Molecular Genetic ◽  
Clinical Manifestations ◽  
Cftr Gene ◽  
Genetic Characteristics ◽  
Missense Variants ◽  
Pathogenic Variants

The variety of clinical manifestations of cystic fibrosis is driven by the diversity of the CFTR gene nucleotide sequence. Descriptions of the clinical manifestations in patients with the newly identified genetic variants are of particular interest.The aim of this study was to describe clinical manifestations of the disease with the newly identified genetic variants.Methods. Data from Registry of patients with cystic fibrosis in the Russian Federation (2018) were used. The data review included three steps — the search for frequent mutations, Sanger sequencing, and the search for extensive rearrangements by MLPA. 38 pathogenic variants were identified that were not previously described in the international CFTR2 database. We selected and analyzed full case histories of 15 patients with 10 of those 38 pathogenic variants: p.Tyr84*, G1047S, 3321delG, c.583delC, CFTRdele13,14del18, CFTRdele19-22, c.2619+1G>A, c.743+2T>A, p.Glu1433Gly, and CFTRdel4-8del10-11.Results. A nonsense variant p.Tyr84* was found in 5 patients (0.08 %). Two missense variants c.3139G>A were found in 2 siblings (0.03 %). The c.4298A>G was found in 1 patient. Other variants were detected in a single patient (0.02 %) each. They included two variants of a deletion with a shift of the reading frame 3321delG and c.583delC, two splicing disorders c.2619+1G>A and c.743+2T>A, three extended rearrangements CFTRdele19-22, CFTRdele13,14del18, and CFTRdel4-8del10-11. The last two variants include 2 rearrangements on one allele, which cause the severe course in two young children. 8 of the 10 variants are accompanied by pancreatic insufficiency (PI). Among patients with p.Tyr84*, one had ABPA, one had liver transplantation, and all had Pseudomonas aeruginosa infection. Nasal polyps were diagnosed in 2 patients with p.Tyr84*, 1 with G1047S, 1 with CFTRdel4-8del10-11, and 1 patient with 3321delG, who also had osteoporosis and cystic fibrosis-related diabetes (CFRD). 2 patients with PI with 3321delG and CFTRdel4-8del10-11 genetic variants, and 1 with PI with p.Glu1433Gly genetic variant had severe protein-energy malnutrition (PEM).Conclusion. Clinical manifestations of previously undescribed CFTR genetic variants were described. 5/10 genetic variants should be attributed to class I, 3/10 – to class 7 of the function classification of pathogenic CFTR gene variants associated with transcription and translation disruptions. Class of the identified missense variants c.3139G>A and c.4298A>G has not been established and requires further functional, cultural, and molecular genetic studies.

Clinical and Genetic Characteristics of Phenylketonuria in Ryazan Region

2021 ◽  
Vol 29 (1) ◽  
pp. 5-12
Author(s):  
Grigorii I. Yakubovskii ◽  
Olga B. Serebriakova ◽  
Alina G. Yakubovskaya ◽  
Nadezhda V. Ruban ◽  
Angelina A. Lyakhovets
Keyword(s):  
Blood Level ◽  
Phenylalanine Hydroxylase ◽  
Clinical Course ◽  
Molecular Genetic ◽  
Residual Activity ◽  
Speech Development ◽  
Genetic Characteristics ◽  
Frequent Mutations ◽  
R408w Mutation ◽  
Pah Gene

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the diseases clinical course, the phenylalanine blood level, and the patients genotype. Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the diseases clinical course, and the patients genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two severe mutations (residual activity of phenylalanine hydroxylase 10%). The second group (n=12) had one severe and one mild mutation (the residual activity of the enzyme 10%). Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federations average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11GA (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the diseases clinical course, and the patients genotype revealed a reliably higher content of amino acid in the first group on retest (32.11.7 mg/% vs. 17.71.5 mg/% in the second group, р0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group. Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the diseases clinical portrait, the phenylalanine blood level, and the patients PAH genotype was revealed.

Molecular Genetic Characteristics of Medieval Populations of the Russian North

2004 ◽  
Vol 40 (1) ◽  
pp. 1-9 ◽  
Author(s):  
E. E. Kulikov ◽  
A. P. Buzhilova ◽  
A. B. Poltaraus
Keyword(s):  
Molecular Genetic ◽  
Genetic Characteristics ◽  
Russian North

scholarly journals PREVALENCE AND MOLECULAR GENETIC PECULIARITIES OF PARENTERAL VIRAL HEPATITIS B AND C AMONG HIVPOSITIVE CITIZENS OF THE FAR EASTERN FEDERAL DISTRICT, INCLUDING THOSE PERSONS SENTENCED TO DEPRIVATION OF FREEDOM

2019 ◽  
pp. 51-55
Author(s):  
E.A. Bazykina ◽  
V.B. Turkutyukov ◽  
O.E. Trotsenko ◽  
V.O. Kotova ◽  
L.A. Balakhonsteva ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Hiv Infection ◽  
Viral Hepatitis ◽  
Molecular Genetic ◽  
Federal District ◽  
Biological Research ◽  
Hiv Positive ◽  
Healthy Population ◽  
Genetic Characteristics ◽  
Viral Hepatitis B

We conducted a comparative analysis of the parenteral viral hepatitis B and C (HBV and HCV) prevalence and their molecular genetic characteristics among prisoners of persons diagnosed with HIV infection (41 samples), HIV-positive free citizens (187 samples) and «conditionally healthy population» with the lack of information about the presence of a diagnosis of chronic viral hepatitis of any etiology and HIV infection (231 samples). Immunological and molecular biological research methods were used. Obtained data analysis showed that the prevalence of infection markers with viruses of parenteral hepatitis was significantly higher in the groups of HIV-positive individuals (imprisoned and freemen). The HBsAg-negative form of the disease was determined among the HIV-positive free population and in the «conditionally healthy population». Over the past 10 years (2009–2018), the proportion of HIV-positive prisoners in custody of people with HCV monoinfection doubled, HBV was increased in 8.7 times. Significant decrease in the combined infection of HBV and HCV of this contingent was found. Given this decrease in the penitentiary system in HIV-positive individuals, the overall burden of HBV infection (both in mono form and coinfection with HCV) significantly (5.3 times) decreased , which can be attributed to successful widespread vaccination against hepatitis B in Russia. The most common HCV genotypes among HIV-positive individuals were 1b and 3a, genotypic structure of HBV prevailed genotype D.

scholarly journals On the study of seizures in newborns and early age children (features of diagnosis and clinical and genetic characteristics of epileptic encephalopathies)

2021 ◽  
pp. 37-50
Author(s):  
V.Yu. Martyniuk ◽  
◽  
T.K. Znamenska ◽  
V.B. Shveikina ◽  
V.A. Galagan ◽  
...  
Keyword(s):  
Young Children ◽  
Metabolic Disorders ◽  
Molecular Genetic ◽  
Nerve Impulse ◽  
Epileptic Seizures ◽  
Short Review ◽  
Epileptic Encephalopathy ◽  
Genetic Characteristics ◽  
Epileptic Encephalopathies ◽  
Metabolic Defects

The article is devoted to the urgent problem of neonatology and pediatric neurology — seizures in newborns and young children. In the work, a short review of the clinical and genetic characteristics of monogenic epilepsy is presented, in particular, the main attention is paid to the variants that begin in neonatal and early childhood. It has been shown that a significant number of epileptic encephalopathies are caused by mutations in genes whose protein products form voltage-dependent (sodium and potassium), ligan(dependent (γ-aminobutyric acid — GABA) channels, the functioning of which ensures the passage of a nerve impulse in neurons of the cerebral cortex. The necessity of including the molecular genetic methods into the algorithm for examining a child with epilepsy, in particular with epileptic encephalopathy, is emphasized. It is noted that congenital metabolic disorders are one of the etiological reasons for the development of epileptic seizures in children, in particular in newborns and young children. It was shown that congenital metabolic disorders have phenotypic manifestations of epileptic encephalopathy. Some curable metabolic defects that are accompanied by seizures, their diagnosis and timely treatment are described. No conflict of interest was declared by the authors. Key words: newborn, epilepsy, epileptic encephalopathy, diagnosis, genetic examination, metabolic defects, review.

Sign in / Sign up

Export Citation Format

Share Document