Introduction.Leukemia accounts for 40 % of all malignant neoplasms under the age of 15 years in children. Determination of the genetic portrait of patients with acute lymphoblastic leukemia (ALL) helps to identify polymorphisms in the genes responsible for the metabolism of drugs included in standard treatment protocols.Materials and methods.51 children with confirmed diagnosis of acute lymphoid leukemia (ALL) were included in the analysis of the frequency of polymorphism of TPMT gene. The detection of polymorphisms TPMT*2, TPMT*3A and TPMT*3 was performed using a set of reagents “AmpliSens® Pyroskrin” & “FARMA-screen-2b”.Results.Polymorphisms in the TPMT gene of 51 patients were found in 6 (11.8 %) children. Of these, 4 patients have variant alleles TPMT*3A and TPMT*3C and 2 patients have only TPMT*3C. Of the 6 patients with TPMT polymorphism, two have a translocation t(12;21).

Хронические миелопролиферативные неоплазмы (ХМН) – клональные заболевания, характеризующиеся нарушением пролиферации миелоидной линии клеток в костном мозге. Для подтверждения диагноза и определения фенотипической формы, ВОЗ рекомендуется проведение молекулярно-генетических исследований. Предполагается, что исследование ДНК, выделенной из костного мозга в парафиновых блоках от тринегативных пациентов с ХМН, позволит выявить соматические мутации (в генах JAK2, CALR, MPL), ассоциированные с ХМН. В данной работе показано, что ДНК из костного мозга в парафиновых блоках от пациентов с ХМН пригодна для генетических исследований.

Соматическая мутация JAK2 c.1849 G>T (V617F) приводит к цитокин-независимому росту клеточных линий костного мозга. Она является одним из диагностических критерий хронических миелопролиферативных неоплазм. Секвенирование по Сэнгеру является золотым стандартом для анализа этой мутации, но имеет низкую чувствительность. Программное обеспечение «Minor Variant Finder» способно обнаружить мутацию при уровне аллельной нагрузки от 5%. Для проверки чувствительности ПО, были взяты ДНК 7-ми пациентов с ХМН с уже известным уровнем аллельной нагрузки. Секвенирование по Сэнгеру и анализ в «Minor Variant Finder» подтвердили заявленную чувствительность ПО.

Background: Myelofibrosis (MF) is a myeloproliferative disease that is characterized by variable life expectancy, cytopenia, splenomegaly, and constitutional symptoms. Although allogeneic stem cell transplantation can be a curative treatment, it carries a high risk of morbidity and mortality (1,2). Ruxolitinib, a JAK2 inhibitor, is a new treatment option which improves symptomatic splenomegaly in patients with intermediate and high risk myelofibrosis. Aims: In this retrospective study we documented our real life clinical experience with ruxolitinib in MF patients. Methods: We reviewed the data of 53 patients with MF who were treated with ruxolitinib. Primary endpoint is to identify the improvement in spleen size and symptoms of the patients. Secondary endpoint was to determine overall survival of the patients, treatment safety and tolerability. Spleen size was measured by using ultrasound examination. Myeloproliferative Neoplasm 10 (MPN-10) disease-specific questionnaire was used to evaluate the symptoms and quality of life.Results: Fifty three patients with a mean age of 63.5 years were evaluated. Mean follow-up time on ruxolitinib treatment was 18.9 ± 17.3 months (range 1-69 months). DIPSS plus score was Int-1 in 33 patients (62.3%), Int-2 in 16 patients (30.2%), high risk in 4 patients (7.5%). Baseline demographic data of the patients were summarized in Table 1. The median subcostal spleen size decreased from 80 (34-272) mm to 49 (0-210) mm in 28 (52%) patients. Median spleen size reduction was 45% (10-100%) in these patients. Spleen size decreased by 35% in 17 (32%) patients (Figure1). In six patients (11 %), there were no change in spleen size. Spleen size increased 29.5% in 12 patients (1.5-85.7%). Percentage of the patients whose spleen length did not change or increase were relatively high in post ET-MF patients compared to patients with primary MF (66% vs. 34 %, respectively, P>0.05). MPN-10 reassessment data within the first 6-12 months was documented in 15 patients and found to be improved in 10 of 15 patients (66%). Hematologic adverse events were found in %77.4 which includes 73.6% anemia, 28.3% thrombocytopenia. Grade 2-3 anemia and grade 3 thrombocytopenia was seen in 50% and 13% of the patients, respectively. Non-hematological adverse events were observed in 11.3% of patients. Overall survival of the cohort was 66.7 ± 46.3(5-206) months. A total of 10 patients died, in three of them the cause of death was leukemic transformation. Summary/Conclusion: Our results which are similar to previous studies show that ruxolitinib is associated with improvement in quality of life and splenomegaly (3). The most important hematological side effects are anemia and thrombocytopenia and non-hematological side effects are acceptable. The main difference of our real-life data from the previous randomized clinical studies is that the majority of our patients had intermediate-I disease. In this real-life data we showed that ruxolutinib is safe and effective in this group of patients.

Background. Parkinson’s disease (PD) is one of the common neurodegenerative diseases. Several genes are known (SNCA, PARK2, PINK1, PARK7 (DJ-1) and LRRK2), mutations in which have a pathological significance in the development of monogenic PD; association with PD of other genes (for example, UCHL1, ATP13A2) requires further study. It is also known, that GBA gene is associated with an increased risk of PD developing.Aim. Analysis of mutations and polymorphisms in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 and GBA genes in patients with PD from Krasnoyarsk region.Material and methods. The 60 patients with sporadic and familial forms of PD were included in the study. The SALSA MLPA Holland P051 and P052 kits («MRC Amsterdam», The Netherlands) were used to detect deletions and duplications in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL, GCH1 genes, as well as point mutations A30P in the SNCA gene and G2019S in the LRRK2 gene. Analysis of the GBA gene was carried out by Senger sequencing.Results. None of the 60 patients had mutations that were searched with the SALSA MLPA Holland P051 and P052 kits. 6 different mutations in the GBA gene were found in 9 out of 60 patients with PD. L444P («severe» PD — associated mutation) — in two patients, D409H («severe» PD — associated mutation) — in one patient, T369M (polymorphism, possibly associated with PD) — in two patients, E326K (polymorphism, possibly associated with PD) — in one patient, V460V (synonymous variant, which is part of the composition of the complex RecNcil mutation (p.L444P; p.A456P; p.V460V) associated with PD) — in two patients and variant C.*92g>A (3’ — UTR polymorphism, possibly associated with PD) — in one patient. Two patients had compound heterozygous carriers of two variants.Conclusion. This paper presents the genetic analysis results of the PD associated genes among patients from the Krasnoyarsk region. No mutations were detected in the PARK2, PINK1, SNCA, ATP13A2, PARK7, LRRK2, UCHL and GCH1 genes. Genetic variants analysis of the GBA gene showed similar frequency in the patients from the Krasnoyarsk region as in European populations.