BACKGROUND:Analysis of immunoglobulin heavy chain gene (IGHV) rearrangements expressed in chronic lymphocytic leukemia (CLL) cells has provided insights into the B-cell receptor (BCR) repertoire in CLL. In more than 40% of CLL patients, (quasi)identical or stereotyped BCR is expressed. The recent data point at the non-stochastic expression of immunoglobulin light lambda (IGLV) or kappa (IGKV) chains as well. Several pairs of IGHV and IGK/LV have been described for some major stereotyped subsets, but most subsets have not been characterized. AIM:To study the IGK/LV gene expression in stereotyped CLL cases. MATERIALS AND METHODS:Analysis was performed in a group of 105 CLL patients with stereotyped BCR. The cases with stereotyped BCRs were identified according to Agathangelidis et al. (2021). The IGHV and IGK/LV gene expressions were studied by a polymerase chain reaction followed by direct sequencing. RESULTS:The expression of the IGK/LV genes in the most presented major stereotyped subsets (#1, #2, #3C3, #4, #6, #28а) was in agreement with the data reported by other authors. For the cases of subsets #5b, #9D1, #9D4, #16, #50, #59, and #77, differences were found. The new data on the IGK/LV gene expression in 55 minor clusters were presented. A number of patterns of the IGK/LV gene expression depending on the phylogenetic clan and mutational status of the IGHV genes have been described. CONCLUSION:The non-stochastic distribution of the IGKV/LV gene expression in the individual stereotyped subsets was confirmed. Taking into account the complementary role of the light chains in antigen recognition by the clonotypic BCRs, it was suggested that the subsets with the heterogeneous IGK/LV expression might be reclassified and divided into separate subgroups based on the IGHV and IGK/LV association.

Summary. CD38 antigen is a negative prognostic marker of chronic lymphocytic leukemia (CLL). The question of what cut-off level of CD38 antigen expression should be considered as prognostically significant, remains debatable. Aim: to evaluate the optimal cut-off level for CD38 antigen in primary untreated CLL patients for the prognosis of disease and its association with the mutational status of immunoglobulin heavy chain genes (IGHV genes). Objects and methods: flow cytometric and molecular-genetic analysis (mutational status of IGHV genes using polymerase chain reaction followed by direct sequencing) were performed in the groups of 106 primary previously untreated CLL patients. Time-to-treatment, progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox regression. Results: The prognostic value of cut-off level CD38 antigen expression ≥ 20% or ≥ 30% does not differ significantly. Lowering of cut-off level to 7% or 5% was unsignificant. The specificity of the evaluation of the mutational status of IGHV genes based on CD38 antigen expression was low, since CD38 expression in almost half of CLL cases with unmutated IGHV genes not differ from CLL cases with mutated IGHV genes. Conclusion: the obtained data confirmed the prognostic value of CD38 antigen expression in patients at the initial stages of disease (A0-AI), primarily for assessing the duration of overall survival.

AIM:The IGHV mutational status is one of the most important markers for chronic lymphocytic leukemia (CLL) prognostication. Lipoprotein lipase (LPL) gene expression was found to correlate with IGHV status and was suggested as its surrogate marker. Recent data reported that LPL expression might be influenced by pivotal signalling pathways in CLL. This study aimed to assess LPL gene expression in relation to key immunogenetic and molecular markers of CLL, including IGHV mutational status, B-cell receptor (BCR) stereotypy, TP53, NOTCH1, and SF3B1 gene mutations. Materials and Methods: Expression of LPL mRNA was measured in peripheral blood mononuclear cells of 73 CLL patients by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). IGHV, NOTCH1, TP53, and SF3B1 gene mutation analysis was performed by PCR amplification and direct sequencing.RESULTS:44 of 73 (60%) CLL cases were categorized as LPL-positive based on the cut-off value established by ROC (receiver operating characteristic) curve analysis. LPL expression was significantly associated with IGHV mutation status (r = 0.684; p < 0.0001) and tended to correlate with presence of NOTCH1 gene mutations (p = 0.113). BCR stereotyped cases showed higher LPL expression values in comparison to unstereotyped cases in the LPL-positive group of patients (p = 0.041). LPL expression was associated with a shorter overall survival in the entire СLL group (median 107 vs 143, p = 0.048) as well as in Binet A patients, albeit with borderline significance (median 139 vs not reached, p = 0.086).CONCLUSION:LPL expression was found to be closely correlated with IGHV gene mutational status and overall survival, proving LPL as prognostic marker in CLL. Our results also indicate a possible relationship between aberrant expression of LPL and BCR- and NOTCH1-dependent signalling pathways.

BACKGROUND:The typical chronic lymphocytic leukemia (CLL) immunophenotype is vital for diagnosis, but the expression of some antigens varies and has prognostic value. There are data that reduced CD20 expression is associated with NOTCH1 and SF3B1 gene mutations.AIM:To determine a high-risk group of CLL patients for prediction of unfavorable NOTCH1 and SF3B1 gene mutations based on immunophenotyping of leukemic cells.MATERIALS AND METHODS:Flow cytometric and molecular-genetic analysis (mutations of NOTCH1, SF3B1, and TP53 genes using the polymerase chain reaction followed by direct sequencing) was performed in a group of 86 previously untreated CLL patients.RESULTS:The immunophenotype of leukemic cells of all examined patients met the criteria of CLL diagnosis. NOTCH1 gene mutations were found in 21 patients (24.4%), and SF3B1 gene mutations - in 7 patients (8.1%). There were no TP53 gene mutations among the examined patients. A decreased number of CD20+CD5+ cells and a downward trend in the relative index of mean fluorescence intensity (iMFI) of CD20+ cells were found in patients with NOTCH1 and SF3B1 gene mutations. Based on the iMFI level (higher and/or lower than 3.0) and the number of CD20+CD5+ cells among all B-cells (higher and/or lower than 50%), we distinguished CLL cases with low and relatively high levels of CD20 antigen expression. Using ROC analysis and the parameter of low CD20 antigen expression, we could predict the presence of NOTCH1 and SF3B1 gene mutations in 73.3 ± 0.06% of patients (p = 0.001). The risk of NOTCH1 and SF3B1 gene mutations in cases with low CD20 antigen expression was 6.96 (95% CI = 2.53-19.18; p = 0.0001). The revealed regularities were statistically significant for patients in whom the diagnosis was established in all Binet - Rai stages except A0-AI.CONCLUSION:Our data confirmed a reduced CD20 expression in CLL patients with NOTCH1 and SF3B1 mutations. In addition, an approach was proposed to identify high-risk CLL patients for prediction of such mutations: previously untreated CLL patients at advanced Binet - Rai stages (BII, CIII, CIV) with a reduced number of double-positive CD20+CD5+ cells in peripheral blood and/or low iMFI of CD20+ cells.

Objective – to investigate the course of B-cell chronic lymphocytic leukemia (CLL) in patients after SARS-CoV-2 virus infection taking into account anamnestic exposure to the ionizing radiation (IR). Methods. The study was performed in a group of 51 CLL patients who were admitted to the Department of Radiation hematology of the National Research Center for Radiation Medicine of NAMS of Ukraine, Kyiv, from January 2020 (the beginning of SARS-CoV-2 epidemic) to August 2023. The group included 19 (37.3 %) clean-up workers of the Chornobyl NPP accident, 15 (29.4 %) inhabitants of radionuclide contaminated areas and 17 (33.3 %) IR nonexposed patients. The diagnosis of CLL was based on clinical history, lymphocyte morphology, and immunophenotypic criteria. Statistical studies were performed using the SPSS software package, version 20.0. Results. The diagnosis of CLL was established for the first time in 14 patients, in seven of them, CLL was diagnosed after 2–17 months after SARS-CoV-2 infection. In contrast to patients who did not suffer from a coronavirus infection, they had pronounced lymphadenopathy, which in some cases was accompanied by hyperleukocytosis, and needed early treatment. Thirteen patients with a previously established CLL were diagnosed with COVID-19 by PCR test. In seven of them (53.8 %) starting treatment was needed, or CLL has progressed. Seven of 51 patients (13.5 %) were vaccinated against SARS-CoV-2. Then, four of them were diagnosed with SARS-CoV-2 infection, confirmed by a positive PCR test, and two patients had a relapse of CLL within 1-2 months after vaccination. Most of patients with signs of the influence of SARS-CoV-2 infection on CLL belonged to sufferers of the Chornobyl NPP accident Conclusions. The clinical features of CLL that developed after SARS-CoV-2 were characterized firstly. The negative impact of SARS-CoV-2 infection on previously established CLL was established. The question about vaccination of CLL patients remains debatable. Key words: chronic lymphocytic leukemia, SARS-CoV-2, Chornobyl NPP accident.

Aggressive disorders have moderate heritability; therefore, identification of genetic influences is important. TheX-linked MAOA gene encoding the MAOA enzyme has a functional polymorphism of 30 bp repeats. in the promoter region (MAOA-uVNTR), which affects aggression. Stressful life events and family misfortune are also known correlates of behavior disorder in children.OBJECTIVE:to investigate the interactive effect of monoamine oxidase-A gene promoter polymorphism (MAOA-uVNTR) and environmental factors on the development of aggressive behavior.MATERIALS AND METHODS:Genotyping of the MAOA-uVNTR polymorphism was performed in 144 boys and girls aged from 10 to 16 years, genotypes were grouped by a high and low transcriptional activity. For the general assessment of the psycho-emotional sphere of children, the projective method «non-existent animal» was used, the indicators and forms of aggression were determined according to the method of A. Bass and A. Darky.RESULTS AND DISCUSSION:It was found the predominant allelic variants of the MAOA gene with 3 (S) and 4 (L) tandem repeats. The presence of close relationships between the dependent variable «aggressive behavior» and the predictor variables: «family disadvantage index» and «MAOA-uVNTR genotype» was established. It has been proven that the presence of the highly active allele (L) in the genotype reduces the chances of developing general aggression, delinquent behavior, physical aggression, open aggression, negativism, and externalization.CONCLUSIONS:The MAOA genotype of the high-activity allele (L) moderated the impact of stressful life events, and the low-activity allele S was associated with increased aggression in girls and boys who experienced severe stress.

OBJECTIVE:to analyze the stereotyped subsets in cohort of Ukrainian chronic lymphocytic leukemia (CLL) patients in general and depending on the ionizing radiation (IR) exposure.METHODS:Analysis was performed in the groups of 118 CLL patients irradiated due to the Chornobyl NPP accident (95 clean-up workers, 17 inhabitants of radionuclide contaminated areas, and 6 evacuees) and 294 IR non-exposed patients. The IGHV (immunoglobulin heavy chain variable region) gene mutational status, mutations of NOTCH1, TP53 and SF3B1 genes were studied by polymerase chain reaction followed by direct sequencing. Associations between clinical and molecular data of patients were analyzed with the SPSS software package, version 20.0.RESULTS:The incidence of stereotyped CLL cases in Ukrainian cohort was high (50.5 %) and comparable in IR-exposed and non-exposed patients. The ratio of major and minor clusters as well as the frequency of individual clusters was comparable with reported data with some exceptions: a low incidence of subset #2; absence of subset #8; high frequency of minor subset #V4|J4.5.6|18|5. The distinctive features of IR-exposed CLL patients found were:1) comparable frequency of stereotyped cases among mutated and unmutated (UM) IGHV genes cases (p = 0.557);2) lack of differences IGHV gene repertoires among stereotyped and heterogeneous cases (p = 0.508); 3) «heterogeneity» of stereotyped cases: all identified stereotyped clusters, with the exception of cluster #1, consisted of one case. Stereotyped cases with expression of UM IGHV clan I genes (except IGHV1-69 gene) were more susceptible to the appearance of NOTCH1 mutations. Patients of cluster #4 were younger, tended to have a longer time-to-treatment period and overall survival (OS) compared to subset #2. Patients of cluster #2 are more likely to have autoimmune hemolytic anemia (AIHA) and SF3F1 mutations. IGHV3-21 expression was associated with worse OS in univariate and multivariate analysis. AIHA was more common in patients with UM IGHV4-59 and IGHV3-11 genes.CONCLUSIONS:The revealed differences in distribution of stereotyped CLL cases in Ukrainian cohort are most likely to reflect variations in the genetic background, environmental factors (including IR exposure), and their interactions in different geographic areas.

Introduction. The course of chronic lymphocytic leukemia (CLL) varied from indolent to rapidly progressive. Stratification of CLL patients into risk groups is based on the stage of disease, the mutational status of immunoglobulin variable region genes (IGHV genes), and mutations of ТР53, NOTCH1, and SF3B1 genes. The frequency of SF3B1 gene mutations increases significantly in the progression of CLL. Aim: to determine the group of CLL patients with increased risk of developing SF3B1 mutations. Material and methods. Analysis was performed on the group of 261 CLL patients. The SF3B1 mutations and IGHV gene mutational status were studied by polymerase chain reaction (PCR) followed by direct sequencing. Results. SF3B1 mutations were identified in 30 patients (11.5%). The frequency of mutations did not differ among primary patients (8.6%) and patients examined before the start of the first line of therapy (9.9%) but increased in relapsed patients (23.8%), p = 0,01. In cases with the expression of IGHV3-21, IGHV3-30, IGHV4-59, and IGHV4-61 genes, regardless of their mutational status, the risk of developing SF3B1 mutations increased 4.97 times (95% CI = 2.21–11.19; p = 0.000047). In addition, stereotypy of the B-cell receptor (cluster #2), the risk of SF3B1 gene mutations increased in 8.65 times (95% CI = 1.66–45.05; p = 0.0027). Conclusion. The expression of individual IGHV genes and the configuration of the B-cell receptor are significant measure the probability of occurrence of SF3B1 gene mutations. Key words: chronic lymphocytic leukemia, SF3B1 gene mutations, IGHV genes, B-cell receptor stereotype

BACKGROUND:Identification of epitopes recognized by leukemic B cells could provide insights into the molecular mechanisms of B cell transformation in chronic lymphocytic leukemia (CLL). The aim of this paper was to compare nucleotide sequences of immunoglobulin heavy chain variable region (IGHV) genes in CLL with known sequences directed against antigens of different origins available in public databases.MATERIALS AND METHODS:Analysis was performed in the groups of 412 unselected CLL patients with productive IGHV gene using polymerase chain reaction followed by direct sequencing.RESULTS:Homology between CLL Ig sequences and antibodies directed against autoantigens was found in 12 patients (2.9%), homology between CLL Ig sequences and antiviral antibodies - in 35 patients (8.5%). Most of these sequences belonged to stereotypical clusters. Among the sequences that have homology to antiviral antibodies, the most prevalent were cases homologous with antibodies against HIV (14 cases, 3.4%) and SARS-CoV-2 antigens (10 cases, 2.4%). None of the patients in our cohort was HIV-infected and the study was conducted before the emergence of SARS-CoV-2 virus.CONCLUSIONS:Suggestions could be made about the possible impact of past infection of SARS-CoV-2 virus on the pathogenesis of CLL. In particular, an increase in the proportion of CLL cases with the expression of some stereotyped BCR and/or an increase of CLL risk in the long-term period after SARS-CoV-2 virus infection is not excluded. This assumption needs to be verified by epidemiological data.

Introduction. Leukemic cells of patients with chronic lymphocytic leukemia (CLL) are characterized by high expression of the lipoprotein lipase (LPL) gene in unmutated (UM) status of the variable region of the immunoglobulin heavy chain (IGHV) genes and low expression of the SORL1 gene. SORL1 protein promotes the degradation of LPL in nervous cells in vitro that has been previously shown. Objective: to study SORL1 gene expression in CLL patients depending on LPL gene expression and mutational status of IGHV genes. Materials and methods. Analysis was performed in the group of 61 CLL patients. The IGHV gene mutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and SORL1 expression was evaluated by Quantitative Real-time PCR. Results. Relative LPL expression levels in CLL samples ranged from 0.5 to 119.5 (mean 23.65 ± 5.19) and correlated with IGHV mutational status (p < 0.01). The average relative SORL1 expression level was 1.71 ± 0.55. No association between SORL1 expression and IGHV mutational status was found (p = 0.358). Among unmutated IGHV cases, negative correlation between LPL and SORL1 gene expression levels was identified (r = -0.764; p = 0.036). Conclusion. The obtained data support the involvement of SORL1 in the post-translational regulation of LPL levels in leukemic cells in CLL. Ketwords: chronic lymphocytic leukemia, lipoprotein lipase, SORL1.

OBJECTIVE:to study clinical-hematological data and expression of the main and alternative transcripts of SORL1 genein chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophe.METHODS:Analysis was performed in the main group of 34 CLL patients irradiated due to the Chornobyl NPP acci-dent (30 clean-up workers, and 4 evacuees) and in the control group of 27 non-irradiated CLL patients. Groups ofpatients were comparable by age, sex, stage of disease, mutational status of IGHV genes. Expression of the main andalternative transcripts of SORL1 gene was evaluated by Quantitative Real-time polymerase chain reaction (PCR). TheIGHV gene mutational status, TP53 and SF3B1 mutations were studied by PCR followed by direct sequencing. Data wereanalyzed with the SPSS software package, version 20.0.RESULTS:Relative expression level of the main transcript of SORL1 gene was low (mean 1.71 ± 0.55, median 0.57),did not correlate with the IGHV gene mutational status, TP53 and SF3B1 mutations, stage of disease. The expressionof B transcript was not detected, F transcript was expressed at a very low level in 9 patients. The average relativeexpression level of SORL1-Δ2 transcript was 14.1 ± 6.04 (median 3.48; range 0.01-90.51). The expression of SORL1-Δ2transcript above the median was more frequent among patients on C stage (p = 0.001), and in patients with unmu-tated IGHV genes was associated with an extremely negative course of CLL (median of overall survival 9 months vs61 months at low expression). Relative expression levels of the main and alternative transcripts of SORL1 gene inpatients of the main and the control groups did not differ.CONCLUSIONS:Our preliminary data suggest that increased expression of SORL1-Δ2 transcript in CLL patients withunmutated IGHV genes can be considered as a negative prognostic marker.

Relevance. One of the most important factors that determine the effective cultivation of soybeans in the Middle Volga region is the use of modern highly productive varieties adapted to growing conditions. To create a competitive variety, it is important to select sources that are adapted to the environmental factors of a particular region.Methods. Field experiments were carried out according to generally accepted methods. All counts and observations were carried out according to the Methodological Guidelines for Studying the Collection of Legumes. In 2016–2019, 36 early maturing and medium early maturing varieties of soybeans of various ecological and geographical origin, as well as breeding material created in local conditions, were studied in the breeding nursery.Results. It was found that the duration of the growing season over the years of study was largely determined by the duration of the flowering — ripening period (r = 0,96). Correlation analysis showed that a significant role in the formation of the yield of soybeans is played by hydrothermal conditions that develop during the generative phase of plant development. There is a high correlation between the level of yield and the average daily temperature and the sum of active temperatures (r = 0,79–0,82) during the flowering — ripening period. In the breeding nursery, the cultivars that most fully realize the genetic potential and reliably exceed the standard in productivity by 12,0–22,0% were identified: k-177, k-445/2 and IHAR-NK 88/2.

BACKGROUND:Expression of lipoprotein lipase (LPL) correlates with unmutated (UM) status of the variable region of the heavy chain of immunoglobulin (IGHV) genes, but the expression level of LPL in UM chronic lymphocytic leukemia (CLL) cases varies significantly.AIM:To study the association of LPL expression with the genetic variants of the TP53 gene since both genes are involved in lipid metabolism.MATERIALS AND METHODS:Expression of LPL mRNA was measured in peripheral blood mononuclears of 45 CLL patients with UM IGHV genes by real-time quantitative reverse transcription polymerase chain reaction. Mutational status of IGHV genes and TP53 genotyping (rs1042522, rs1642785, rs17883323, rs2909430, rs145153611, rs113530090, rs12947788, rs12951053, and rs17878362) were performed by polymerase chain reaction amplification followed by direct sequencing.RESULTS:Observed CLL patients were divided on groups with low (11.17 ± 2.66) and high (275.48 ± 39.37) LPL expression. In CLL patients with UM IGHV genes and low LPL expression we found an increased frequency of rs1042522 G (p = 0.0036), rs1642785 C (p = 0.0001), and rs17878362A2 alleles (p = 0.0091). The possible functional significance of these changes is discussed.CONCLUSION:Some polymorphic variants of TP53 may be genetic modifiers for LPL expression level in CLL leukemic B-cells. Further research is required in a larger cohort to confirm these findings.

The mutational status of the variable region of the immunoglobulin heavy chain (IGHV) genes remains the most significant prognostic factor in chronic lymphocytic leukemia (CLL) patients. However, the groups of mutated (M) and unmutated (UM) patients are also heterogeneous, and additional markers are used for a more accurate prognosis. The aim of our work was to determine the prognostic value of the signs of antigen selection determined by BASELINe statistics in M IGHV sequences of CLL patients. Clinical data, IGHV gene configuration, TP53, NOTCH1, SF3B1 mutations were analyzed in 127 CLL patients with M IGHV sequences. The median OS of patients with negative selection in the framework regions (FWRs) of IGHV genes was 120 months compared to 202 month in other CLL patients (P = 0.016). In multivariate Cox regression analysis Binet stage C vs A + B (P < 0.0001), SF3B1 mutations (P < 0.0001), negative selection in the FWRs (HR P = 0.007), and age >= 65 years (P = 0.034) were powerful adverse prognostic factors for OS in CLL patients with M IGHV genes. These preliminary data suggest that the signs of antigen-driven selection may be used as a prognostic factor in CLL patients with M IGHV genes in combination with other markers.

Objective The aim of this study was a retrospective analysis of clinical manifestation and treatment outcome of the nasal form of transmissible venereal tumours (TVT). Material and methods Twelve dogs suffering from nasal TVT were included in this study. Patients with primary genital lesions were excluded from the study. Signalment, physical examination and laboratory findings, results of further diagnostics, and treatment results were recorded in all patients. Results The study population comprised 9 male and 4 female dogs with an (estimated) age ranging from 3 to 7 years. With one exception all dogs originated from Ukraine. Symptoms of nasal TVT included sneezing, nasal bleeding (all cases), skull infiltration (9 cases), oronasal fistulas (9 cases) and cutaneous fistulas (5 cases). Animals received vincristine sulfate at 0.7 mg/m(2) i.v. weekly. The treatment course consisted of 4-9 cycles (median 5 cycles). Complete remission was achieved in all cases. All dogs were disease-free during the follow-up period (median 23.5 months, range 12-56 months). All patients tolerated the treatment very well. Clinical significance In conclusion, our data suggest that nasal TVT can have a good response to vincristine treatment. TVT should be considered as a differential diagnosis in sneezing dogs with nasal discharge or bleeding especially in young dogs and in dogs with suspected nasal tumours, even in countries without a stray animal population.

OBJECTIVE:to determine the association between the expression of lipoprotein lipase (LPL) and c-MYC genes inperipheral blood cells of chronic lymphocytic leukemia (CLL) patients affected by the Chornobyl catastrophedepending on the mutational status of IGHV genes.METHODS:Analysis was performed in the group of 69 CLL patients irradiated due to the Chornobyl NPP accident (58clean-up workers of 1986 year, 6 inhabitants of radionuclide contaminated areas, and 5 evacuees). The IGHV genemutational status was studied by polymerase chain reaction (PCR) followed by direct sequencing. LPL and c-MYCexpression was evaluated by Quantitative Real-time PCR. Data were analyzed with the SPSS software package, version 20.0.RESULTS:Relative LPL expression levels in CLL samples ranged from 0 to 1663.5 (mean 138.47 ± 30.69, median 26.1).A strong correlation between individual LPL expression levels and IGHV mutational status was found (r = 0.684;p < 0.0001). The average relative c-MYC expression level was 5.7 ± 0.87 (median 2.86; range 0-48.5). No association between c-MYC expression and IGHV mutational status was found. Among unmutated IGHV cases, a correlationbetween LPL and c-MYC gene expression levels was identified: r = 0.351; p = 0.013.CONCLUSIONS:Our data confirm the dominant concept that unmutated IGHV CLL cases are more sensitive to the actionof proliferative stimuli compared to mutated IGHV CLL cases. This is manifested by an increase in the expression ofa functionally significant LPL gene, is one for the strongest negative prognostic markers in CLL.

BACKGROUND:A number of epidemiological studies have shown an elevated radiation-associated risk for chronic lymphocytic leukemia (CLL). The aim of the paper was to analyze immunoglobulin heavy variable chain (IGHV) rearrangement and IGHV usage in CLL cases associated with ionizing radiation (IR) exposure.MATERIALS AND METHODS:Samples of 76 clean-up workers of Chornobyl Nuclear Power Plant accident of 1986 (the main group) and 194 non-exposed patients (the control group) were analyzed. Two groups of CLL patients were comparable by gender (all patients were male), age, and place of residence (rural or urban).RESULTS:Some features of IR-associated CLL cases as compared to CLL cases in patients without history of IR exposure were revealed. Among unmutated IGHV sequences, IGHV1 genes were less commonly used (29.4% vs 48.6%; p = 0.018), while the frequency of IGHD6 genes was higher (23.5% vs 10%; p = 0.029). The unmutated IGHV sequences did not use IGHD3-16 gene (0% vs 7.9%, p = 0.038). Mutated IGHV sequences were less frequently expressed IGHV3 genes (44% vs 68.5%; p = 0.037) due low representation of IGHV3-21 (4% vs 11.1%) and IGHV3-23 (0% vs 11.1%) genes; did not use IGHD3-22 gene (0% vs 18.5%, p = 0.025); and have signs of positive selection in the HCDR regions (Σ = 0.5029 ± 0.155 vs -0.0539 ± 0.14; p = 0.013).CONCLUSIONS:The revealed differences in IGHV gene usage and B-cell receptor structure in the main and the control groups of CLL patients indirectly indicate a change in the spectrum of antigens associated with CLL under IR exposure. The possible antigenic drivers associated with CLL associated with IR exposure are discussed.

Summary. Some clinical and biological features indicating an unfavorable course of the disease were found in ionizing radiation (IR) — related chronic lymphocytic leukemia (CLL) patients. The MYC proto-oncogene is considered to contribute to CLL pathogenesis. Increased MYC copy number is associated with poor prognosis in CLL. Aim: To investigate the frequency of MYC gene copy number amplification in IR-exposed CLL patients and relate the findings to the MYC mRNA levels, the presence of unfavourable prognosis mutations (TP53, SF3B1, NOTCH1), and patient's outcome. Materials and Methods: The analysis of MYC copy number was carried out by real-time quantitative polymerase chain reaction (PCR) in 70 IR-exposed CLL patients. The MYC mRNA expression was measured by real-time quantitative reverse transcription PCR. Results: Increased MYC gene copy number was present in 5.7% of cases. There was a statistically significant association between increased MYC copy number and increased MYC mRNA (p < 0.014). Additionally, somatic deletion in MYC locus was found in one patient. Most of patients (80%) with detected MYC aberrations were previously untreated, suggesting that these lesions might occur early in the course of the disease. The MYC aberrations were found mutually exclusive with high risk TP53 and SF3B1 mutations, while one case was identified, where MYC amplification and NOTCH1 mutation coincided simultaneously. Regarding clinical outcome, the MYC aberrations were associated with a shorter time to first treatment (3 vs 25 months, p = 0.008) as well as reduced overall survival (60 vs 139 months). Conclusion: Our data suggest that MYC aberrations might be an early event in IR-related CLL and contribute to aggressive disease development in the absence of high risk TP53 and SF3B1 mutations.

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disor-ders in the victims due to the Chornobyl accident, the pathogenesis of which is insufficiently studied.Objective is to identify the neuropsychiobiological mechanisms of the formation of the remote affective and cog-nitive disorders following exposure to ionizing radiation taking into account the specific gene polymorphisms.Design, object and methods of research. The retrospective and prospective cohort study with the external andinternal control groups. The randomized sample of the male participants in liquidation of the consequences of theaccident (Chornobyl clean-up workers, liquidators) at the Chornobyl nuclear power plant (ChNPP) in 1986-1987(n = 198) recruited from the Clinico-epidemiological registry (CER) of NRCRM aged 39-87 (M ± SD: 60.0-8.5 years)with the external irradiation dose ranged 0.6-5900.0 mSv (M ± SD: 456.0 ± 760.0 mSv) was examined. The compar-ison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with thecorresponding age and sex (the external control group). The internal control group included the liquidators irradi-ated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnairesand tests, neuropsychological methods (including the Wechsler Adult Intelligence Scale (WAIS) with premorbid IQ(pre-IQ) assessment), neuropsychiatric and psychophysiological methods (quantitative EEG (qEEG) and the audito-ry cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin trans-porter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and vari-ation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and riskanalysis were used.Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-relatednature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with theirradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of theverbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment atdoses > 0.3 Sv is dose-dependent (r = 0.4-0.7; p = 0.03-0.003). Affective disorders (depression) and neurocogni-tive deficit are more severe at higher doses of irradiation (> 50 mSv). In the left posterior temporal region(Wernicke's area) the qEEG indices changes become dose-dependent at doses greater than 0.25-0.3 Sv. The dis-turbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The car-riers of intermediate and low-level genotypes (LА/S, LА/LG, LG/LG, LG/S, S/S) of the serotonin transporter gene SLC6A4have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive andstress-related disorders.The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earli-er (Log-Rank Test = 4.43, p = 0.035) in comparison with the carriers of the high-performance genotype LА/ LА.Conclusions. The radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere ofthe human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of post-radiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these dis-orders associated with ionizing radiation depending on the certain gene polymorphisms.