Identifying the stage of new CLL patients using TK, ZAP-70, CD38 levels

Serum thymidine kinase (TK), zeta-associated protein of 70 kDa (ZAP-70) and CD38 levels have been shown to be correlated with survival in chronic lymphocytic leukaemia (CLL). Aim: To investigate the possible correlations between TK, ZAP-70 and CD38 levels as prognostic markers in new diagnosed Rai stages of CLL patients. Methods: 120 CLL patients were enrolled. ELISA was used to measure serum TK level, flow cytomerty — to determine ZAP-70 and CD38 expression applying ZAP-70 Kit and monoclonal antibody to CD38, respectively. Results: Significantly higher levels of TK were found in the high progression group of CLL patients that corresponded to stage II (Rai classification). An elevated level of TK, CD38 and ZAP-70 together was also found in the II stage. The coefficient of correlation between CD38 and ZAP-70 is reliable (p < 0.001). There is also a correlation between the level of TK and the disease stage (p < 0.05). Other parameters do not show this correlation. Conclusion: The determination of TK, ZAP-70 and CD38 together allows patients susceptible to a possible stage of the disease, to be identified. Estimation of the factors at an early stage of the disease may allow an earlier commencement of treatment

Past and present thermokarst lake dynamics in the Yedoma Ice Complex region of North-Eastern Yakutia

Thermokarst lakes are typical components of the yedoma-alas dominated relief in the coastal lowlands of North- Eastern Yakutia and formed as a result of thawing Late Pleistocene ice-rich Yedoma Ice Complex (IC) deposits. The aim of our study is to estimate thermokarst lake area changes from the early Holocene onwards based on RS data. The decrease of thermokarst lake area from the early Holocene, taking into account total alas depression areas, is as much as 81-83 %. Modern climate warming has led to a general trend of thermokarst lake area decrease. Lake drainage occurs mostly on elevated sites with high Yedoma IC fraction while lake area increase is typical for low-lying areas with a small Yedoma IC fraction. The area increase of thermokarst ponds on flat, boggy yedoma surfaces indicates ice wedge degradation in response to rising summer air temperatures and precipitation

Generic imatinib in the treatment of chronic myeloid leukemia: two years’ experience in latvia

Background: Imatinib is tyrosine kinase inhibitor (TKI) and as a targeted anti-cancer agent has significantly changed chronic myeloid leukemia (CML) prognosis and patient survival. Currently TKI is the main therapy in CML Philadelphia chromosome-positive (Ph-positive) cases. When generics of imatinib appeared in the pharmaceuticals market, reimbursement policies in many countries switched to using generics or encouraged use of generic imatinib to lower the expenses. Cost savings were substantial; however, for doctors and CML patients the efficacy, safety and quality of generic imatinib were an issue of concern. Objective: Since the global number of CML patients, who in the future will have to switch from original imatinib to generic imatinib, is high, the aim of study was to monitor, whether during 24 months of generic imatinib usage patients maintain the achieved major molecular response (MMR) or whether the treatment results are inferior. Methods: We conducted a retrospective study, which included CML patients, who were above 18 years of age and who until May 2013 had used at least for 2 years (24 months) the original imatinib, and following that used at least for 24 months one of the generic imatinib medicines. In 2013, before switching to generic imatinib, all patients had reached MMR in accordance with European LeukemiaNet (ELN) Guidelines. Every three months blood count, BCR-ABL fusion gene (BCR-ABL), biochemical analysis and side effect were monitored. Results: Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. Nobody was switched to second line generation TKI. During observation period neither haematological, nor non-hematological toxicity was found. Conclusion: Our study proved that CML patients, who had achieved MMR by original imatinib therapy, retained MMR during 24 months of generic imatinib therapy. This demonstrates that generic imatinib is not inferior to original imatinib. As to expenses, the annual costs of generic imatinib are lower by 96%, which is a significant benefit to health-care financing

Mycoplasma Diversity in Arctic Permafrost

© 2016, Springer Science+Business Media New York.Viable bacterial cells and its genetic material can be stably maintained in Arctic permafrost for a long geological time. Because of the seasonal melting of permafrost strata, it cannot be excluded an access to the surface of ancient highly invasive species with increased pathogenicity. Mycoplasmas are very successful pathogens in humans, mammals, birds, insects, and plants, with high genome plasticity and ability to avoid immune response of host organism. The metagenomic approach allowed us to predict mycoplasma diversity in the Arctic permafrost. The number of mycoplasma DNA fragments in soil deposits of comparable age (∼30,000 years) and origin (the late Pleistocene Ice Complexes) is not so abundant compared with other microorganisms, but it is enough for a chance in the presence of living mycoplasmal cells in permafrost. DNA fragments of human, animal, insect, and plant pathogens were identified. The “ubiquitous” mycoplasma Acholeplasma laidlawii is the undisputed leader in the number of identified sequences in all three metagenomes. It may indicate a higher adaptive capacity and more powerful metabolic potential of A. laidlawii among Mollicutes

Draft Genome Sequence of Antarctic Methanogen Enriched from Dry Valley Permafrost

A genomic reconstruction belonging to the genus Methanosarcina was assembled from metagenomic data from a methane-producing enrichment of Antarctic permafrost. This is the first methanogen genome reported from permafrost of the Dry Valleys and can help shed light on future climate-affected methane dynamics

Peripheral blood lymphocyte phenotype of ZAP-70⁺ and ZAP-70⁻ patients with B-cell chronic lymphocytic leukaemia

Background: Up to now, the immune status of chronic lymphocytic leukemia (CLL) patients in association with the expression of zeta-chain-associated protein kinase 70 (ZAP-70) in leukemic cells has not been evaluated. Aim: The aim of this work was the study of the peripheral blood (PB) T-lymphocyte phenotypes in ZAP-70-positive (ZAP-70⁺) and ZAP-70-negative (ZAP-70⁻) untreated patients with CLL. Materials and Methods: ZAP-70⁻, CD25-, CD3-, CD4-, and CD8-positive lymphocytes were enumerated by flow cytometry in PB of 120 untreated CLL patients. CD8+, CD3+CD4+ and CD3+CD25+ cells were counted for the non-leukemic lymphocytes. Results: The patients were distributed into two groups: the ZAP-70⁺ group of high CLL progression (n = 61), and the ZAP-70− group of low CLL progression (n = 59). In the ZAP-70⁺ group, the ratio CD4/CD8 (0.33 ± 0.62; p = 0.001) and the numbers of the CD3+ (34.8 ± 8.1%; p = 0.01), CD3+CD4+ (24.4% ± 4.8; p = 0.001), and CD3+CD25+ (6.2 ± 0.91%; p = 0.001) lymphocytes were reduced and the percentage of the CD8+ cells (73.1 ± 4.6%; p = 0.0001) was above the norm. In the ZAP-70− group, the number of the CD3+CD4+ cells (36.9 ± 6.1%; p = 0.001) was within the norm, but the numbers of the CD8+ (11.3 ± 1.1%; p = 0.0001) and CD3+ (41.2 ± 5.3%; p = 0.05) lymphocytes were reduced; the ratio CD4/CD8 (3.26 ± 0.88; p = 0.001) and the percentage of the CD3+CD25+ cells (27.1 ± 3.4%; p = 0.0001) were above the norm. Conclusions: Our data show that the increased CD4/CD8 ratio, caused by the reduced number of the CD8+ lymphocytes, and the increased number of CD3+CD25+ cells are characteristic for the ZAP-70− group (slow progressing) of untreated CLL patients. In ZAP-70⁺ patients, the CD4/CD8 ratio was significantly below the norm indicating an active disease process. Results of our study contribute to identification of CLL patients with different prognosis in routine diagnostic/prognostic procedures. Key Words: chronic lymphocytic leukemia, ZAP-70, immune status, CD4/CD8 ratio, regulatory T cell

Cryogenic Displacement and Accumulation of Biogenic Methane in Frozen Soils

Evidences of highly localized methane fluxes are reported from the Arctic shelf, hot spots of methane emissions in thermokarst lakes, and are believed to evolve to features like Yamal crater on land. The origin of large methane outbursts is problematic. Here we show, that the biogenic methane (δ13C ≤ −71‰) which formed before and during soil freezing is presently held in the permafrost. Field and experimental observations show that methane tends to accumulate at the permafrost table or in the coarse-grained lithological pockets surrounded by the sediments less-permeable for gas. Our field observations, radiocarbon dating, laboratory tests and theory all suggest that depending on the soil structure and freezing dynamics, this methane may have been displaced downwards tens of meters during freezing and has accumulated in the lithological pockets. The initial flux of methane from the one pocket disclosed by drilling was at a rate of more than 2.5 kg C(CH4) m−2 h−1. The age of the methane was 8–18 thousand years younger than the age of the sediments, suggesting that it was displaced tens of meters during freezing. The theoretical background provided the insight on the cryogenic displacement of methane in support of the field and experimental data. Upon freezing of sediments, methane follows water migration and either dissipates in the freezing soils or concentrates at certain places controlled by the freezing rate, initial methane distribution and soil structure

Chemokine Receptors CCR1 and CCR2 on Peripheral Blood Mononuclear Cells of Newly Diagnosed Patients with the CD38-Positive Chronic Lymphocytic Leukemia

Chemokines and their receptors direct migration and infiltration of immune cells. CCR1 and CCR2 maintain sequence similarity and respond to a number of the same chemokines secreted in lymphoid organs. Expression of CD38 on leukemic cells has been associated with poor clinical outcomes in patients with chronic lymphocytic leukemia (CLL) and is considered as the negative predictor of progression. In our study of newly diagnosed CLL patients, which included 39 CD38-positive and 22 CD38-negative patients, CCR1 and/or CCR2 were always detected, using flow cytometry, on the peripheral blood (PB) CD19+CD5+ lymphocytes in patients with >30% of the CD38+ CD19+CD5+ lymphocytes (n = 16). Spearman’s rank correlation analysis determined correlations between the frequency of the CCR1- and CCR2-expressing PB CD19+CD5+ lymphocytes and the frequency of the CD38-positive CD19+CD5+ lymphocytes (rs = 0.50 and rs = 0.38, respectively). No significant correlations were observed between ZAP70 mRNA expression levels in PB mononuclear cells and the frequency of the circulating CCR1+ or CCR2+ CD19+CD5+ lymphocytes. Further association studies are needed to verify prognostic relevance of the CCR1/CCR2 expression on leukemic cells in CLL patients at diagnosis. We suggest that CCR1/CCR2 signaling pathways could represent attractive targets for development of CLL anti-progression therapeutics