BACHELORS’ INDEPENDENT WORK: STAGES OF ORGANIZATION THROUGH THE APPLICATION OF SIMULATION TECHNOLOGY

Purpose of the study: The article analyses the problem of the students’ independent work organization within the framework of simulation technology. We placed the main emphasis on the stages of the organization of University students’ self-study of a foreign language. Moreover, we assess how the application of simulation technology raises the efficiency of students’ independent work. Methodology: We wrote the article on data collected from surveys in 2018. Students from the Orenburg State University participated in this research. This study used the quantitative approach of experimental research by dividing students into two groups, experimental and control ones. We collected the data through questionnaires, interviews, and documentation. We used statistical methods of survey data processing for analysis, among them descriptive analysis, correlation, and factor analyses. Main Findings: Simulation technology is an active and innovative tool in education. The organization of students’ independent work within the frame of the simulation technology promotes the development of initiative and self-sufficient students. It contributes to the improvement of the subjective bachelors’ qualities such as strength of linguistic knowledge, linguistic and reflexive skills. Besides, students understood the importance of independent work in the educational process. Applications of this study: The material of the study can be useful for university teachers and students and a wide range of readers interested in a new developing and innovative way of learning in the education of students. Novelty/Originality of this study: In this article, we described the organization of students’ independent work within the frame of the simulation technology. The results can be used by university teachers as an innovative tool for students learning. This method of intensification of learning activity can lead to the creation of an own model of teaching the students

Translocation t(1;11)(p32;q23) with MLL-EPS15 fusion gene formation in acute leukemias: a review and 6 new case reports. Approaches to minimal residual disease monitoring

We performed clinical and laboratory characterization of patients with rare translocation t(1;11)(p32;q23) leading to MLL-EPS15 fusion gene formation. Study cohort consisted of 33 primary acute leukemia (AL) cases including 6 newly diagnosed and 27 patients previously described in literature. Among study group patients t(1;11)(p32;q23) was found most frequently in infant AL cases (median age 8 months). In acute lymphoblastic leukemia (ALL) male/female ratio was 1:3, in acute myeloid leukemia (AML) it was 1:1. Additional cytogenetic aberrations in 38 % of patients were revealed. The most frequent breakpoint position in EPS15 gene was intron 1. Four different types of MLLEPS15 fusion gene transcripts were detected. Primers-probe-plasmid combination for MLL-EPS15 fusion gene transcript monitoring by realtime quantitative polymerase chain reaction (RQ-PCR) was developed and successfully applied. In 3 patients RQ-PCR was done on genomic DNA for absolute quantification of MLL-EPS15 fusion gene. High qualitative concordance rate (92 %) was noted between minimal residual disease data obtained in cDNA and genomic DNA for MLL-EPS15 fusion detection.</p

Immunophenotypic investigation of infant acute lymphoblastic leukemia

Aim of the study – immunophenotype description of infant acute lymphoblastic leukemia (ALL). 64 patients (29 boys and 35 girls) with acute leukemia (AL) aged from 0 to 11 months were included in the current study. ALL was found less frequently in infants than in older children (67.19 % and 87.69 %, respectively). BI-ALL was the most common immunological ALL type (60.46 %) in infant ALL, while BII-ALL was notably less frequent compared with other age groups (30.23 %). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD10, CD20, CD45, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD10- and CD20-negativity, high CD45, CD15, CD65 and NG2 expression were immunophenotypic signatures of MLL-rearranged infant ALL, although NG2 had the highest diagnostic efficacy. High CD34 and CD65 expression was frequently associated with presence of MLL-AF4 fusion gene. Thus infants’ B-cell precursor ALL immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ ALL allows predicting presence of MLL rearrangements and NG2 is the most applicable single marker.</p

Immunophenotypic investigation of infant acute myeloid leukemia

Aim of the study – characterization of immunophenotype in infant acute myeloid leukemia (AML). 90 patients (40 boys and 50 girls) with acute leukemia (AL) aged up to 365 days were included in the current study. AML was found more frequently in infants than in older children (26.67 % and 10.83 % respectively; p = 0.0002). Significant immunophenotypic differences were observed in patients with and without MLL gene rearrangements. Number of cases in those tumor cells expressed CD99, CD61, CD133, CD15, NG2 varied between MLL-positive and MLL-negative groups. CD61-negativity, high CD99, CD15, CD133 and NG2 expression were immunophenotypic signatures of MLLrearranged infant AML, although CD99 and NG2 had the highest diagnostic efficacy. Thus infants’ AML immunophenotype differs significantly due to the presence of MLL gene rearrangements. Diagnostic immunophenotyping of infants’ AML allows predicting presence of MLL rearrangements by either CD99 or NG2 expression.</p

Flow cytometric minimal residual disease monitoring in children with acute lymphoblastic leukemia treated by regimens with reduced intensity

191 consecutive unselected children with acute lymphoblastic leukemia aged from 1 to 16 years were enrolled in the study. Bone marrow samples were obtained at the time of initial diagnostics as well as at days 15 (n = 188), 36 (n = 191), and 85 (n = 187) of remission induction. Minimal residual disease (MRD) was assessed by 6–10-color flow cytometry. Flow cytometry data at day 15 allowed distinguishing three patients groups with significantly different outcome (p ˂ 0.0001): 35.64 % patients with MRD &lt; 0.1 % represented 5-year event-free survival (EFS) of 100 %; 48.40 % cases with 0.1 % ≤ MRD&lt; 10 % had EFS 84.6 ± 4.2 %; 15.96 % patients with very high MRD (≥ 10 %) belonged to group with poor outcome (EFS 56.7 ± 9.0 %). At the end of remission induction (day 36) 36 children (18.85 %) with MRD higher than 0.1 % had significantly worse outcome compared to remaining ones (EFS 49.4 ± 9.0 and 93.5 ± 2.1 % respectively; p ˂ 0.0001). From a clinical standpoint it is relevant to evaluate both low-risk and high-risk criteria. Multivariate analysis showed that day 15 MRD data is better for low-risk patients definition while end-induction MRD is the strongest unfavorable prognostic factor

SIGNIFICANCE OF ETV6-RUNX1 FUSION GENE TRANSCRIPT DETECTION IN PEDIATRIC B-CELL PRECURSOR ACUTE LYMPHOBLASTIC LEUKEMIA WITH TRANSLOCATION t(12;21)(p13;q22)

Introduction. Translocation t(12;21)(p13;q22) is one of the most common structural genetic abnormalities in childhood acute lymphoblastic leukemia (ALL). It cannot be detected by conventional G-banding, so a reverse-transcriptase polymerase chain reaction (RT-PCR) or fluorescent in situ hybridization are used for this purpose.The aim of the study was to evaluate the prognostic significance of qualitative and quantitative detection of ETV6-RUNX1 fusion gene transcript at various time points in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients.Materials and methods. ETV6-RUNX1 fusion gene transcript was revealed by both reverse-transcriptase PCR and quantitative real-time PCR (RQ-PCR) in 34 out of 166 (20.5 %) children with BCP-ALL. Qualitative ETV6-RUNX1-positivity at days 36 and 85 led to unfavorable outcome (lower event-free survival –EFS and higher cumulative incidence of relapse – CIR). While ETV6-RUNX1 status at day 15 did not allow to divide patients with different outcomes. By ROC curve analysis we determined threshold levels (TL) for ETV6-RUNX1/ABL1 ratio at days 0, 15, 36 and 85. Afterwards we adjusted obtained results to 10-fold scale.Results. So practically applicable TL were as follows 500.0 %, 1 %, 0.1 % и 0.01 % for days 0, 15, 36 and 85, respectively. EFS and CIR were both worse in patients with ETV6-RUNX1/ABL1 ratio equal or above defined TL. Moreover, initial ratio ≥500,0 % corresponded to delayed blast clearance at days 15 and 36. We showed good qualitative (84.8 %) and quantitative (R2 = 0.953) concordance between ETV6-RUNX1/ABL1 ratio and MRD data obtained by flow cytometry at days 15, 36, 85. Of note, defined TL for ETV6-RUNX1/ABL1 at days 15, 36, 85 were equal to prognostically important levels for flow cytometry MRD.Conclusion. Thus, qualitative detection and quantitative value of ETV6-RUNX1 fusion gene transcript showed prognostic significance in the course of treatment in children with BCP-ALL. Based on these results we propose standardization approaches for Moscow – Berlin ALL study group

Detection of 11q23 (MLL) rearrangements in infant acute lymphoblastic leukemia

117 cases of infant acute lymphoblastic leukemia without Down syndrome (aged from 1 to 365 days) were included in the current study.Rearrangements of 11q23 (MLL) were revealed in 74 (63.2 %) patients. Among this group the most common rearrangement was t(4;11) q21;q23)/MLL-AF4 detected in 63.5 % cases, less frequently was found t(11;19)(q23;p13)/MLL-MLLT1 (in 18.9 % cases), t(10;11) p12;q23)/MLL-MLLT10 and t(1;11)(p32;q23)/ML L-EPS15 (each one in 6.8 %), t(9;11)(p22;q23)/MLL-MLLT3 in 2.7 %. Children under 6 months of age had significantly higher incidence of 11q23 (ML L) rearrangements in comparison with infants olde r than 6 months (84.0 % vs. 47.8 %, p &lt; 0.001). P atients with translocations 11q23 (ML L) more frequently had BI-A LL and less frequently BII-ALL than children without these rearrangements (p &lt; 0.001 f or both). Fusion gene transcript w as sequenced in 26 ML Lrearranged cases. Depending on breakpoint position within ML L and partner genes we detected 7 differ ent types of ML L-AF4 fusion gene transcript, 3 types of MLL-MLLT1, 2 types of MLL-EPS15. The most common fusion site within MLL gene was exon 11, detected in 14 (53.8 %) patients.</p

Relation between genomic dna breakpoints in mll gene and treatment outcome in infants with acute leukemia

Цель: Оценить влияние локализации точки разрыва в геномной ДНК гена MLL на прогноз острых лейкозов (ОЛ) у детей первого года жизни. Методы: В исследование было включено 68 детей первого года жизни (29 мальчиков и 39 девочек с медианой возраста 4,8 мес.) с MLL-позитивными острым лимфобластным лейкозом (ОЛЛ) (n = 46), острым миелоидным лейкозом (ОМЛ) (n = 20) и ОЛ смешанной линейности (n = 2). Результаты: 5-летняя бессобытийная выживаемость (БСВ) детей первого года жизни с ОЛЛ, включенных в исследование MLL-Baby, с точкой разрыва в интроне 11 ДНК гена MLL (n = 29) была статистически значимо ниже, чем у пациентов c локализацией точек разрыва, начиная с интрона 7 по экзон 11 (n = 17; 0,16 ± 0,07 и 0,38 ± 0,14; p = 0,039), а кумулятивная вероятность развития рецидива была значительно выше в группе с точкой разрыва в интроне 11 (0,74 ± 0,09 и 0,52 ± 0,17; p = 0,045). В то же время многофакторный анализ показал, что единственным значимым фактором, связанным с неблагоприятным прогнозом, остается сохранение минимальной остаточной болезни (МОБ) в точке наблюдения 4 протокола MLL-Baby (отношение опасности 5,994; 95%-й доверительный интервал 2,209–16,263; p < 0,001). У 22 пациентов с ОМЛ связи между прогнозом и локализацией точки разрыва в ДНК гена MLL не выявлено. Заключение: Наличие точки разрыва в интроне 11 гена MLL у детей первого года жизни с ОЛЛ, получавших лечение по протоколу MLL-Baby, вело к статистически значимо более низким показателям БСВ и более высокой кумулятивной вероятности развития рецидива. Однако в многофакторной модели риска это нивелировалось сохранением МОБ в точке наблюдения 4. У детей первого года жизни с ОМЛ взаимосвязи между локализацией точки разрыва в ДНК гена MLL и прогнозом не выявлено.Aim: To evaluate the relation between genomic DNA breakpoints in MLL and translocation partner genes (TPG) and clinical parameters of infant AL. Methods: 68 infants (29 boys and 39 girls with median age of 4.8 mo) with MLL-rearranged acute lymphoblastic leukemia (ALL) (n = 46), acute myeloid leukemia (AML) (n = 20) and mixed phenotype acute leukemia (MPAL) (n = 2) were included in the current study. Results: 5-year EFS was significantly lower in patients with breakpoints in intron 11 (n = 29) in comparison to patients with breakpoint localized from intron 7 to exon 11 (n = 17) (0.16 ± 0.07 vs 0.38 ± 0.14, p = 0.039). While cumulative incidence of relapse was remarkably higher in the first group of patients (0.74 ± 0.09 vs 0.52 ± 0.17, p = 0.045). Although in Cox regression model including breakpoint location in intron 11 together with age, immunophenotype, initial white blood cell count, initial CNS involvement, type of MLL rearrangements, absolute blast number at day 8 of dexamethasone profase, minimal residual disease (MRD) at time point 4 (TP4) of MLL-Baby protocol, the only significant covariate was the presence of MRD at TP4 (HR 5.994, 95% CI 2.209–16.263, p < 0.001). In 22 AML patients there was not any correlation between breakpoint location and treatment outcome. Conclusion: Breakpoints in intron 11 of MLL gene led to significantly worse outcome in infants with ALL, treated by MLL-Baby protocol, although this parameter was overcome by MRD-positivity at TP4. The latter was the only independent covariate in multivariate analysis. Our data provide additional information of molecular genetic features of MLL-rearranged infant AL