Changes in Glycanic Determinants of Lymphocytes Membranes in Peripheral Blood in Patients with B-Cell Chronic Lymphocytic Leukemia under Antitumor Therapy

The purpose of the study was to study the nature of changes in the exposure of surface glycans of peripheral blood lymphocytes in patients with B-cell chronic lymphocytic leukemia under conditions of antitumor therapy. Materials and methods. We studied the features of exposure of surface glycotopes of peripheral blood lymphocytes in patients with B-cell chronic lymphocytic leukemia under conditions of antitumor therapy using a set of seven lectins labeled with FITC and monoclonal antibodies to Tn-antigen- FITC for the detection of Tn antigen and CD43 exposure on blood lymphocytes. Cytostatic therapy included cyclophosphamide, vincristine (oncovin), prednisolone. Data were recorded on a Beckman Coulter EPICS flow cytometer. The results were processed using FCS3 Express. Results and discussion. The number of lymphocytes of healthy donors with a positive reaction to ConA, PHA-L, SNA, MAA-II and α1-acid glycoprotein amounted to 16.0±3.0%, 23.0±2.3%, 15.0±1.5%, 25.0±1.8% and 15.0±1.3%, respectively. The number of LABA-, UEA I-positive lymphocytes was 0.90±0.03% and 2.9±0.2%, respectively, and there was no binding to antibodies to Tn- and CD43-antigens. In the blood of patients with chronic lymphocytic leukemia, the level of ConA-, SNA- and MAA-II-positive lymphocytes increased relative to control by 2.2, 3.7 and 2.6 times, respectively. The number of LABA- and UEA I-positive lymphocytes in patients with chronic lymphocytic leukemia increased by 11 (p <0.01) and 23 (p <0.001) times and amounted to 10.5±0.5% and 67.5±5.5% respectively. The number of lymphocytes with CD43 antigen on their surface increased by 72 times, and the Tn antigen increased by 80 times. Cytostatic therapy reduced the level of LABA- and UEA I-positive lymphocytes by almost half, and MAA II-positive cells and lymphocytes interacting with antibodies to CD43 and Tn antigen by a third. The level of PHA-L-positive lymphocytes in the blood of chronic lymphocytic leukemia patients after undergoing alkylating therapy increased by 18.0±2.0% and almost did not differ from those obtained in the control group. Conclusion. 1. In chronic lymphocytic leukemia patients, the structure of glycoconjugates in peripheral blood lymphocytes changes, manifested in increased exposure of L-fucose, α-mannose and N-acetylneuraminic acid, which is confirmed by a significant increase in relation to the control of the number of ConA-, SNA-, MAA-II-, LABA I-positive cells. 2. Patients with chronic lymphocytic leukemia showed a significant increase in the number of lymphocytes, in which the markers of carcinogenesis CD43 and Tn antigens were found. 3. Cytostatic therapy significantly reduced the level of LABA-, UEA I- and MAA II-positive cells, as well as partially Tn- and CD43-antigen-positive lymphocytes, which indicates its positive effect on the treatment of chronic lymphocytic leukemia

Glycobiom Lymphocytes Surface Study of Patients with B-Cell Chronic Lymphocytic Leukemia

The purpose of the study was to investigate the intensity of exposure of peripheral blood lymphocyte surface glycans in patients with B-cell chronic lymphocytic leukemia by measuring the density of lectin- or antigen-positive epitopes under antitumor therapy in order to evaluate it for a more reasonable selection of qualitative and quantitative composition of therapy. Materials and methods. The objects of the study were blood lymphocytes of patients with chronic lymphocytic leukemia (n=15) aged 58-66 years before and after a course of standard chemotherapy according to the COP scheme. The control group consisted of healthy volunteers (n=15) aged 55 to 65 years. Isolation of lymphocytes was performed by a modified method of A. Boyum. Polyclonal antibodies to α1-acid glycoprotein and fibronectin were used. Exposure to Tn antigen and CD43 on blood lymphocytes was determined with secondary antibodies to mouse immunoglobulins conjugated to FITC (Millipore, USA). To study the exposure of glycans on the surface of lymphocytes, we used a set of seven lectins labeled with FITC. Data recording was performed on a Beckman Flower EPICS flow cytometer. Processing of the results was done using the program FCS3 Express. Results and discussion. Compared with the group of hematologically healthy donors on the surface of lymphocytes in patients with chronic lymphocytic leukemia, a 20-fold increase in the density of exposure to ConA epitopes, 10 times – UEAI- and SNA-positive epitopes were shown; MAA II epitope, Tn, and CD43 antigen densities were increased 100-fold (p <0.01). Exposure densities of MAA II-, Tn-, and CD43-positive epitopes on the plasma membrane of lymphocytes in patients with chronic lymphocytic leukemia receiving alkylation therapy decreased 10-fold relative to treatment data, but remained 10-fold higher than in the group of healthy hematologists. Conclusion. On the plasma membranes of lymphocytes in patients with chronic lymphocytic leukemia, the density of exposure of mannose and neuraminic acid residues was significantly increased. COP therapy reduced the density of these epitopes to control values. A significant increase in the density of carcinogenesis markers – Tn- and CD43-antigens on the plasma membranes of lymphocytes in patients with chronic lymphocytic leukemia has been shown. COP therapy provided only a partial decrease in their density, which indicates the insufficient effectiveness of COP therapy, its inability to completely stop the oncological process in patients with chronic lymphocytic leukemia

Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sword

Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.Conclusions Haematological malignancies (blood cancers) patients are more vulnerable to COVID-19 disuse severity and mortality. Un fortunately mRNA vaccine seem to be less effective with weak immune response and insufficient level of generated antibodies in this category of patients. Therefore we suggest all trans retinoic acid is a good candidate as mRNA COVID-19 vaccine adjuvant via inducing LZTFL1 gene in CD4Tcells and this activation could improve the immune response and increase the level of the generated antibodies. Moreover LZTFL1 gene in CD4 T cells is not associated with increasing risk of COVID-19 infection because of absence of its enhancer(The risk allele of the SNP, rs17713054 A) in immune cells according to oxford recent study. In addition to all trans retinoic acid could inhibit CCAAT/enhancer binding protein beta motif that is generated by The risk allele of the SNP, rs17713054 A

Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sward

Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.

Could the candidate causal gene (LZTFL1) identified by Oxford University scientists, which doubles the risk of COVID-19-related respiratory failure, be used to boost the Weak immunogenicity of COVID-19 mRNA vaccines in patients with B-cell chronic lymphocytic leukemia (CLL)???. A double edged sward

Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of severe infections due to disease- and treatment-related immunodeficiency. As a result, patients with hematologic malignancies have been given priority for primary COVID-19 vaccination. Unfortunately, many studies have suggested that patients with B-cell chronic lymphocytic leukemia (CLL) who have been fully vaccinated can develop severe and often fatal complications. Therefore, adjuvants that can induce mRNA vaccine efficacy are desperately needed for this category of patients with haematological malignancies. A recent, study by Oxford University scientists showed that leucine zipper transcription factor-like 1(LZTFL1), as a candidate causal gene and its enhancer the rs17713054 A risk allele was significantly responsible for the twofold increased risk of respiratory failure from COVID-19 associated with 3p21.31.By using sequence analysis, the risk allele generates a second CCAAT/enhancer binding protein beta (CEBPB) motif in the enhancer. Moreover, neither LZTFL1 variants found in T cells nor B cells are responsible for increasing death risk from COVID-19 infection according to oxford study. Here, we propose attestable hypothesis that trans retinoic acid could enhance the immune response in vaccinated patients with B-cell chronic lymphocytic leukemia (CLL) according to the recent findings of Oxford scientists by inducing the casual gene(LZTFL1) in CD4 T cells and inhibiting (CEBPB) motif.Conclusions Haematological malignancies (blood cancers) patients are more vulnerable to COVID-19 disuse severity and mortality. Un fortunately mRNA vaccine seem to be less effective with weak immune response and insufficient level of generated antibodies in this category of patients. Therefore we suggest all trans retinoic acid is a good candidate as mRNA COVID-19 vaccine adjuvant via inducing LZTFL1 gene in CD4Tcells and this activation could improve the immune response and increase the level of the generated antibodies. Moreover LZTFL1 gene in CD4 T cells is not associated with increasing risk of COVID-19 infection because of absence of its enhancer(The risk allele of the SNP, rs17713054 A) in immune cells according to oxford recent study. In addition to all trans retinoic acid could inhibit CCAAT/enhancer binding protein beta motif that is generated by The risk allele of the SNP, rs17713054 A

Individual features of the pharmacokinetics of fludarabin phosphate in the treatment of patients with chronic lymphocytic leukemia

Fludarabine is a purine antimetabolite with a pronounced immunosuppressive effect. The inhibitory effect of fludarabine depends on its concentration in blood plasma. In addition, the phenotypic characteristics of patients affect the pharmacokinetic and pharmacodynamic profile of the drug, which necessitates a personalized approach to the dosage regimen. The chromatography-mass spectrometric method for the quantitative determination of 2-fluorine in blood plasma was developed for studying the individual parameters of pharmacokinetics of the international non-proprietary name (INN) fludarabine in patients with B-cell chronic lymphocytic leukemia during the standard course. Such method for the quantitative determination of 2-fluorine in blood plasma was developed and validated in accordance with international requirements. Significant individual variability of the main pharmacokinetic parameters in patients with B-cell chronic lymphocytic leukemia with a single oral administration of the drug with INN fludarabine at a dose of 40 mg/m2 was established, so the coefficient of variability Cmax was 42 %, Tmax — 92 %, AUC0-t — 45 %, Kel — 23 %, T1/2 — 26 %. It should be noted that there is a high interindividual variability of fludarabine, for example, 24 hours after taking the study drug, the maximum and minimum plasma concentrations of the fludarabine metabolite 2-fluoro-ara-A in different in patients with B-cell chronic lymphocytic leukemia differed 9 times. Individual variability of pharmacokinetic parameters characterizing absorption (Cmax/AUC0-t) and total clearance of the active metabolite of fludarabine is statistically significantly associated with a combination of gender and anthropometric factors.

Stationary distribution and extinction for a stochastic two-compartment model of B-cell chronic lymphocytic leukemia

In this paper, we study the dynamical behavior of a stochastic two-compartment model of [Formula: see text]-cell chronic lymphocytic leukemia, which is perturbed by white noise. Firstly, by constructing suitable Lyapunov functions, we establish sufficient conditions for the existence of a unique ergodic stationary distribution. Then, conditions for extinction of the disease are derived. Furthermore, numerical simulations are presented for supporting the theoretical results. Our results show that large noise intensity may contribute to extinction of the disease.

Difficulties of anemia diagnosis in patients with B-cell chronic lymphocytic leukemia

Cytopenia commonly occurs in case of chronic lymphocytic leukemia. It can either precede the diagnosis of chronic lymphocytic leukemia or appear at any time during the disease. Autoimmune hemolytic anemia, immune thrombocytopenia, and partial red cell aplasia are most often found among cytopenias in chronic lymphocytic leukemia. At the same time, the development of cytopenia may be associated with the displacement of normal hematopoiesis cells by tumor lymphocytes. It is very important to accurately diagnose and identify the cause of cytopenia in chronic lymphocytic leukemia, since the prognosis and therapy differ significantly.