Resistance to chemotherapy is an obstacle to the successful treatment of oncohematological malignances. Failure of therapeutic treatment may be due to the development of multidrug resistance (MDR), the mechanisms of which include upregulation of membrane-resident transporters that efflux chemotherapeutic drugs from tumor cells. Deregulation may occur at different levels: gene or protein expression or function depletion. Childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) cells and chronic lymphocytic leukemia (CLL) cells of adults were studied. ABCB1 (P-gp) and ABCG2 (BCRP) expression were determined by flow cytometry, rhodamine 123 (Rho123) and mitoxantrone were used for functional activity study of MDR proteins, sensitization of leukemic cells to drugs was quantified by methyl thiazolyl tetrazolium (MTT) assays. Appropriate gene expression was determined using semi-quantitative RT-PCR. No differences between expression of P-gp and BCRP and genes in primary and relapsed acute leukemia (AL) cells as well as in de novo and treated CLL samples were established. Higher expression of P-gp and BCRP proteins was detected in CLL lymphocytes compared to blast cells. Increased P-gp protein expression and function was detected in cells of CLL patients who had more aggressive therapy regimen. Doxorubicine, rubomycinum and L-asparaginase resistance correlates with P-gp overexpression and increased function in pediatric AL whereas vincristine resistance might be associated with P-gp protein expression in AL samples and impared P-gp function in CLL lymphocytes only. A tendency for the decreased doxorubicin cytotoxic activity was shown in BCRP-overexpressing cells both in children and adults leukemia. Multifactorial ANOVA showed that P-gp/MDR1 and BCRP as well as their function could not be used as unconditional and universal predictors of leukemia cell drug resistance in vitro. These results suggest that studied MDR transporter-proteins have a limited role per se in vitro and admittedly in vivo drug resistance estimated in leukemia patients or it is not yet fully understood unless would not be studied in aggregate. In any event, the expression and function studies of the proteins under investigation when singularly considered do not have a crucial significance for impact on drug resistance evaluation in all leukemia patients.
The main goal of this investigation was to evaluate the abnormal T-cell immunity in cleanup workers who took part in the cleanup after the Chernobyl accident in 1986. Peripheral blood mononuclear cells (MNCs) of apparently healthy cleanup workers (n = 134) were used to analyze the phenotype and proliferative response to mitogens in vitro. Evaluation of the MNC phenotype of cleanup workers did not reveal a significant disturbance in the T-cell subpopulation content except for an increase in CD3+CD16+56+ (NKT) cells. Immunophenotyping of phytohemagglutinin (PHA)-activated MNCs demonstrated suppression of CD4+ T-cell propagation and augmentation of CD8+ T-cell propagation in vitro compared to control individuals. DNA synthesis in the MNCs of cleanup workers was markedly inhibited after activation for 3 days with suboptimal concentrations of PHA, pokeweed mitogen and PMA. In contrast to control individuals, the monocytes of cleanup workers were able to stimulate the proliferation of T cells from healthy individuals but inhibited the proliferation of T cells from cleanup workers. This study affords a better understanding of the response of MNCs to stimulation with suboptimal concentrations of PHA and provides an approach to a more accurate analysis of the immunological disorders found after exposure to radiation from Chernobyl-related activities.
Background:In the context of significant advances in the treatment of hematological diseases using the method of autologous hematopoietic stem cell transplantation (auto‐HSCT), the number of patients requiring early vaccination against pneumococcal infection increases worldwide. Current guidelines indicate the early initiation of pneumococcal vaccination starting from 3 months after HSCT. Still, the topical issue is the determination of the earliest optimal dates for the start of vaccination after transplantation, taking into account the dynamics of immunological recovery.Aims:The aim of this study was to determine the optimal timeline for the onset of vaccination with conjugated pneumococcal vaccine in patients with multiple myeloma after auto‐HSCT.Methods:The immune response to the conjugated pneumococcal vaccine is based on the T‐dependent (CD4+) activation of B‐cells, what was taken into account when estimating the timing of immune reconstitution after auto‐HSCT in candidates for vaccination.An immunological study using flow cytometry was performed in 37 adult patients with multiple myeloma prior to the auto‐HSCT procedure, as well as on days +30, +60, +90, +180 after transplantation.Results:After auto‐HSCT, the level of naive B‐cells returns to its original value by the 60th day from transplantation (Kruskal‐Wallis test 41.97; P < 0.001), shown on Fig. 1. At the same time, the level of CD4 + cells did not fall below 200 cells/μl starting from day +30, what indicates the effectiveness of early vaccination with T‐dependent vaccines in this category of patients with immunosuppression. Dendritic cells (DC1 and DC2) are restored in parallel by the 30th day from auto‐HSCT (Kruskal‐Wallis test 25.78; P <0.001 for DC‐1 cells and Kruskal‐Wallis test 11,17; P <0.025, respectively), what confirms the basis for the early vaccination with conjugated pneumococcal vaccines in this category of patients.Summary/Conclusion:The obtained data allows planning the introduction of the first dose of the conjugated pneumococcal vaccine 60 days after autologous HSCT, with the perspective of introducing an individualized vaccination calendar based on immunological parameters. It is also necessary to further implement immunization programs for immunocompromised patients, especially in hematology and cancer setting with the participation of a multidisciplinary team of specialists.image
0,65 (0,36-0,73) vs 1,05 (0,67-1,4) % и 0,039 (0,028-0,056) vs 0,063 (0,049-0,076) × 10 9 кл./л соответственно (р = 0,0009, р = 0,003), а также относительной и абсолютной численности плазмоцитоидных дендритных клеток -0,055 (0,04-0,085) vs 0,09 (0,05-0,12) % и 0,0038 (0,0021-0,0054) vs 0,005 (0,0035-0,007) × 10 9 кл./л соответственно (р = 0,0197, р = 0,0414 Introduction. Diagnosis of the kidney transplant cellular rejection in the long-term after transplantation remains a challenge. Usual surrogate markers are not enough sensitive and specific. Rejection is an immune reaction to donor alloantigens. The kidney transplant biopsy to diagnose a dysfunction is an invasive procedure with the incidence of complications about 12.6% and can lead to transplant loss. In this regard, the search of immunological biomarkers for early noninvasive and accurate diagnosis of kidney transplant rejection is an actual task. Material and methods. This is a report of the observational retrospective single-center, comparative case-control study in two groups involving 44 patients who underwent kidney transplantation. The first group (REJ) included the patients with the chronic graft dysfunction caused by a biopsy-confirmed late cellular rejection (22 patients). The second group (STA) included the recipients who had no dysfunction in the posttransplant period (22 patients). Flow cytometry of peripheral blood cells was performed to identify immunophenotyping markers of late cellular rejection after kidney transplantation (we determined subpopulations of T, B lymphocytes, and dendritic cells).Results. As a result of our work, we found significant differences in the absolute count of effector memory T cells making (0.36-0.73) vs. 1.05 (0.67-1.4) % and 0.039 (0.028-0.056) vs. 0.063 (0.049-0.076 , respectively (р = 0.0009, р = 0.003). The numbers of plasmacytoid dendritic cells were also different between the study groups: 0.0038 (0.0021-0.0054) vs. 0.005 (0.0035-0.007) × 10 9 cell/L for an absolute count (р = 0.0414), and 0.055 (0.04-0.085) vs. 0.09 (0.05-0.12
The contents of CD8(+), CD4(+)CD8(+), CD3(+)HLA-DR(+), CD8(+)INF-gamma (+) T cells, and natural killers (CD16(+)56(+)) and NK/T cells (CD16(+)56(+)CD3(+)) increase after 7-day culturing in the presence of interleukin-2. The number of apoptotic cells and cells in S-, and G(2)+M phases of the cell cycle also increased. Interleukin-6 predominantly induced proliferation of CD3(+)HLA-DR(+) T cells and G(2)+M mitotic cells.
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