Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by the malignant transformation of bone marrow-derived myeloid progenitor cells with extremely short survival. To select the optimal treatment options and predict the response to therapy, the stratification of AML patients into risk groups based on genetic factors along with clinical characteristics is carried out. Despite this thorough approach, the therapy response and disease outcome for a particular patient with AML depends on several patient- and tumor-associated factors. Among these, tumor cell resistance to chemotherapeutic agents represents one of the main obstacles for improving survival outcomes in AML patients. In our study, a new prognostic scale for the risk stratification of AML patients based on the detection of the sensitivity or resistance of tumor cells to chemotherapeutic drugs in vitro as well as MDR1 mRNA/P-glycoprotein expression, tumor origin (primary or secondary), cytogenetic abnormalities, and aberrant immunophenotype was developed. This study included 53 patients diagnosed with AML. Patients who received intensive or non-intensive induction therapy were analyzed separately. Using correlation, ROC, and Cox regression analyses, we show that the risk stratification of AML patients in accordance with the developed prognostic scale correlates well with the response to therapy and represents an independent predictive factor for the overall survival of patients with newly diagnosed AML.

Simultaneous quantitative measurement of mRNA of the WT1, BAALC, EVI1, PRAME and HMGA2 genes in whole blood samples reflects the specific pathological proliferative activity in acute leukemia and their ratio is promising as a diagnostic marker. The transcriptome profile of acute leukemia cells is usually assessed using NGS or microarray techniques after a preliminary procedure for isolation of mononuclear cells. However, the results of using the multiplex PCR reaction for the simultaneous determination of all above mRNAs in whole blood samples have not been published so far. Determination of mRNA of WT1, BAALC, EVI1, PRAME and HMGA2 genes in venous blood level samples by multiplex RT-PCR. The study included 127 blood samples from patients who diagnosis of acute leukemia was subsequently confirmed. In the comparison group, 87 samples of patients without oncohematological diagnosis were selected, including 31 samples (K1) with a normal blood formula and 56 samples (K2) with a violation of the cellular composition - anemia, leukocytosis and thrombocytopenia. RNA isolation and reverse transcription were performed using the Ribozol-D and Reverta-L kits (TsNIIE, Russia). Determination of the mRNA expression level of the WT1, BAALC, EVI1, PRAME and HMGA2 genes by multiplex real-time PCR using a homemade multiplex PCR kit. The mRNA level was characterized by high interindividual variation and did not correlate with the rate of circulating leukocytes or blood blasts. Expression of WT1 mRNA was observed in whole blood only in one patient from the control group and in 112 (88%) patients with leukemia and was combined with a decrease in the level of HMGA2 mRNA expression and BAALC mRNA values. In contrast to the control groups, patients with leukemia had higher levels of BAALC mRNA in AML and ALL, increased PRAME mRNA in AML and APL, but lower levels of HMGA2 in APL.

Background. The annual reporting forms for malignant neoplasms do not provide for the division of lymphomas into variants. In international publications and statistical reference books of the Russian Federation, variants of non-Hodgkin’s lymphomas (NHL) are also not separated. For these reasons, a detailed assessment of the epidemiology of NHL in Russia is difficult, and data for individual variants of the disease are not provided.Purpose: to present the clinical and epidemiological characteristics of Diffuse Large B-cell Lymphoma (DL BCL ) in Novosibirsk according to the data of the City Hematology Center (CHC).Material and Methods. A retrospective analysis of primary medical documentation (case histories, outpatient charts, and immunohistochemical study reports) of 271 patients with DL BCL was performed in the period from January 1, 2013 to December 31, 2018.Results. The calculated registered primary morbidity and mortality from DL BCL in Novosibirsk for the analyzed years fluctuated slightly. The average incidence and mortality rates were 2.85 and 1.98 per 100,000 population, respectively. When analyzing the dynamics of the prevalence of DL BCL in Novosibirsk, a positive trend of annual increase in the indicator was revealed: 1.87 times over the past 6 years. In men, the tumor developed 2.6 years earlier than in women. In General, the risk of getting DL BCL after 50 years was 3 times higher than at the age of 30 years. Among patients diagnosed with primary lymphoma who underwent treatment at the Hematology department of CHC, half of the patients had DL BCL .Evaluation of the clinical characteristics showed a pronounced severity of the analyzed cohort.Conclusion. The updated quantitative and qualitative indicators of clinical and epidemiological characteristics of DL BCL in Novosibirsk for 2013–18 were obtained. These indicators can be used for further monitoring, development and implementation of measures for the prevention, diagnosis and treatment of this form of hemoblastosis.

Abstract Background Acute myeloid leukemia (AML) is the most common acute leukemia in adults, and chemotherapy remains the most commonly used treatment approach for this group of hematological disorders. Drug resistance is one of the predictors of unfavorable prognosis for leukemia patients. Aim The purpose of this study was to perform a retrospective analysis of the survival rate in AML patients according to age, tumor status, and chemotherapy regimen received and to analyze the therapy response of AML patients depending on the treatment received, initial responsiveness of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis and expression of immunological markers. Methods The survival of AML patients (n = 127) was analyzed using the Kaplan‐Meier method. Drug sensitivity of tumor cells of AML patients (n = 37) and the expression of immunological markers were evaluated by the WST test and flow cytometry, respectively. Correlation analysis was performed using Spearman's rank order correlation coefficient. Results We found the treatment regimen to be the defining factor in the patient survival rate. In addition, the initial responsiveness of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis correlated with the therapy response of AML: patients with high tumor cell sensitivity to particular cytotoxic drugs demonstrated a good response to treatment including these drugs, and patients with initial resistance of tumor cells to a particular chemotherapeutic agents and received it according to the clinical protocols demonstrated a poor response to antitumor therapy. Correlations of drug resistance in leukemic cells with the expression of immature and aberrant immunophenotype markers as established unfavorable prognostic factors confirm our assumption. Conclusion The evaluation of the responsiveness of tumor cells to chemotherapy in vitro at diagnosis can be a useful tool for predicting the response of leukemia patients to planned chemotherapy.

The genome-wide sequencing data of more than 1200 Diffuse Large B-cell Lymphomas (DLBCL) samples of the CBioPortal database for Genomic cancer were analyzed. We also performed our own full-exome sequencing of 7 samples of DLBCL with relapses in the central nervous system (CNS). Characteristics associated with a high level of secondary CNS involvement in lymphoma were selected. Differences were obtained in the BCR/NF-kB genotypes (MYD88, CD79B) and chromatin remodeling system (ARID1A, SMARCA4).

Проанализированы данные полногеномного секвенирования более 1200 образцов пациентов с диффузной В-крупноклеточной лимфомой (ДВККЛ) базы CBioPortal for Cancer Genomics. Также выполнено собственное полноэкзомное секвенирование 7 образцов ДВККЛ с рецидивами в ЦНС. Выделены характеристики, ассоциированные с высоким риском вторичного вовлечения ЦНС при лимфоме. Значимые различия в частоте мутаций между подвыборками с поражением ЦНС в рецидиве и без вовлечения ЦНС были получены по генам BCR/NF-kВ пути (MYD88, CD79B) и системы ремоделирования хроматина (ARID1A, SMARCA4). The genome-wide sequencing data of more than 1200 Diffuse Large B-cell Lymphomas (DLBCL) samples of the CBioPortal database for Genomic cancer were analyzed. We also performed our own full-exome sequencing of 7 samples of DLBCL with relapses in the central nervous system (CNS). Characteristics associated with a high level of secondary CNS involvement in lymphoma were selected. Differences were obtained in the BCR/NF-kB genotypes (MYD88, CD79B) and chromatin remodeling system (ARID1A, SMARCA4).

Multidrug resistance (MDR) is a major challenge in leukemia treatment. The objective of this study was to identity predictors of MDR to allow for rapid and economical assessment of the efficacy of planned antitumor therapy for leukemia patients. The study included 113 patients with acute and chronic leukemias. Prior to antitumor therapy, we measured the sensitivity of tumor cells of patients to the panel of chemotherapeutic drugs, together with MDR1 mRNA and P-glycoprotein (P-gp) expression as one of the mechanisms of MDR, and compared these data with the response to therapy. The scales for leukemia patients according to therapy response, drug sensitivity of tumor cells, MDR1 mRNA and P-gp levels, and the presence of unfavorable immunological and cytogenetic markers were introduced for subsequent correlation analysis. We show that the drug resistance of tumor cells of leukemia patients estimated in vitro at diagnosis correlates with a poor response to chemotherapy and is usually combined with aberrant and immature immunological markers, cytogenetic abnormalities, and a high expression of MDR1 mRNA and P-gp. All together, these factors indicate unfavorable prognosis and low survival of leukemia patients. Thus, the sensitivity of tumor cells to chemotherapeutic drugs measured in vitro at diagnosis may have prognostic value for individual types of leukemia.