scholarly journals Gene expressions involved in immune system control and serum CA125 content in polycythemia vera. Tap

2020 ◽  
Vol 42 (1) ◽  
Author(s):  
Do Thi Trang ◽  
Nguyen Thi Xuan
Keyword(s):  
Immune System ◽  
Polycythemia Vera ◽  
Immune Tolerance ◽  
Blood Cells ◽  
Myeloproliferative Neoplasms ◽  
Tyrosine Phosphatase ◽  
White Blood Cells ◽  
System Control ◽  
Gene Expressions ◽  
Gene Group

Polycythemia Vera (PV) is a slowly progressing blood cancer associated with myeloproliferative neoplasms. The disease is characterized by an abnormal proliferation of three cell types including red blood cells, white blood cells and platelets and a symptom of pruritus caused by release of itching agents of activated mast cells. The enhanced expression of several genes involved in immune system control including CTLA-4, PD-1 and LAG3 are linked to activation immune tolerance. Klotho gene has anti-aging, anti-inflammation and anti-cancer functions. The SHP gene group belongs to the tyrosine phosphatase protein signaling family that regulates cancer cell proliferation through maturation, migration and apoptosis and includes two main genes, SHP-1 and SHP-2. The increased serum content of cancer antigen CA125 is considered as a cancer marker of several blood and hematopoietic disorders. In this study, we conducted experiments to determine mRNA expression of above genes in PV patients by realtime-PCR and CA125 concentration by ELISA. Results showed that expression of klotho, LAG3, CTLA-4 and PD-1 genes was decreased in PV patients, indicating that the immune tolerance was inactivated in PV patients. CA125 concentration was significantly increased in PV patients compared to healthy individuals and interestingly, there was a positive association among three patients, who having increased CA125 concentration and biochemical indicators including LDH, AST and ALT. The results in this study provide an important reference document for further studies that serve for the early detection of PV disease. 

scholarly journals Critical requirement for Stat5 in a mouse model of polycythemia vera

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3539-3549 ◽  
Author(s):  
Dongqing Yan ◽  
Robert E. Hutchison ◽  
Golam Mohi
Keyword(s):  
Polycythemia Vera ◽  
Blood Cells ◽  
Myeloproliferative Neoplasms ◽  
White Blood Cells ◽  
Strong Support ◽  
Primary Myelofibrosis ◽  
Blood Parameters ◽  
Critical Function ◽  
Critical Requirement ◽  
Multiple Signaling

The JAK2V617F mutation has been identified in most cases of Ph-negative myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Expression of JAK2V617F results in constitutive activation of multiple signaling molecules/pathways. However, the key signaling downstream of JAK2V617F required for transformation and induction of MPNs remains elusive. Using a mouse genetic strategy, we show here that Stat5 is absolutely required for the pathogenesis of PV induced by Jak2V617F. Whereas expression of Jak2V617F in mice resulted in all the features of human PV, including an increase in red blood cells, hemoglobin, hematocrit, white blood cells, platelets, and splenomegaly, deletion of Stat5 in the Jak2V617F knockin mice normalized all the blood parameters and the spleen size. Furthermore, deletion of Stat5 completely abrogated erythropoietin (Epo)–independent erythroid colony formation evoked by Jak2V617F, a hallmark feature of PV. Re-expression of Stat5 in Stat5-deficient Jak2V617F knockin mice completely rescued the defects in transformation of hematopoietic progenitors and the PV phenotype. Together, these results indicate a critical function for Stat5 in the pathogenesis of PV. These findings also provide strong support for the development of Stat5 inhibitors as targeted therapies for the treatment of PV and other JAK2V617F-positive MPNs.

Leukocytosis Can Predict Thrombotic Events in Myelofibrosis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5191-5191
Author(s):  
Laura Coutinho Vassalli ◽  
Emilia Carolina Malafaia ◽  
Maria L. Chauffaille ◽  
Daniella Kerbauy
Keyword(s):  
Polycythemia Vera ◽  
Blood Cells ◽  
Myeloproliferative Neoplasms ◽  
Thrombotic Event ◽  
White Blood Cells ◽  
Jak2 V617f ◽  
The Other ◽  
Jak2 V617f Mutation ◽  
Increased Risk ◽  
V617f Mutation

Abstract Thrombotic events are the main complication of Philadelphia-negative chronic myeloproliferative neoplasms (MPN). In polycythemia vera (PV) and essential thrombocythemia (ET), risk factors for thrombosis are well established, such as age greater than 60 years and previous thrombosis. However, the role of JAK2 V617F mutation and leukocytosis at diagnosis as risk factor for thrombosis is still controversial. Our aim was to identify factors related to the risk for thrombotic events in the studied population.This study is a retrospective non-interventional cohort. All of the analyses were performed using the database of 142 patients with MPN regularly followed at the Hematology Division (at UNIFESP-SP) from 1992 to 2014. Diagnosis was established according to WHO criteria. We analyzed the JAK2 V617F mutation, hemoglobin (g/dL), hematocrit (%), white blood cells (x109/L) and platelets (x109/L) at the diagnosis and DIPSS-Plus risk score (International Working Group for Myelofibrosis Research and Treatment, 2009). These variables were associated with thrombotic event at any time.Of the 142 patients, 54 had diagnosis of PMF, 28 of PV, 33 of ET and 27 of post-essential thrombocythaemic myelofibrosis (post ET MF) or post-polycythaemic myelofibrosis (post-PV MF). This last group was included in myelofibrosis group for statistical purposes. Thrombotic events were more frequent in PV patients (39.2%), followed by ET (33.3%), and PMF (20.9%). From those which JAK2 mutation was obtained, it was positive in 92.4% of PV patients, 62% of PMF and 50% of ET. In none of the three groups, the presence of JAK2 V617F mutation was related to increased risk of thrombosis. In myelofibrosis, leukocytosis was higher among thrombotic patients (median of 13.7 in thrombotic group versus 9.7x 109/L; p 0.0379). None of the other parameters, hemoglobin, hematocrit, platelets and DIPSS-Plus were statistically significant. In ET, the hemoglobin level at diagnosis was significantly higher in the presence of thrombosis (mean of 14.57 in thrombotic group against 13.03 g/dL in the non-thrombotic one, p 0.0428). The other parameters, hematocrit, white blood cells and platelets were not relevant. The median WBC in the thrombotic group was 9.4 and in the non-thrombotic one 9.3 x109/L. Finally, in polycythemia vera, none of the variables were related to thrombosis. Among the studied population, leukocytosis was increased in patients with thrombotic event in MF. Thus, monitoring leukocyte count in MF is essential to predict thrombosis risk and should be further studied in order to define therapeutic goals in these patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Angiogenic parameters and the risk factors for thrombosis in polycythemia vera

2018 ◽  
Vol 72 ◽  
pp. 627-633
Author(s):  
Joanna Boinska ◽  
Grażyna Gadomska ◽  
Katarzyna Ziołkowska ◽  
Karolina Woźniak ◽  
Alicja Bartoszewska-Kubiak ◽  
...  
Keyword(s):  
Risk Factors ◽  
Polycythemia Vera ◽  
Myeloproliferative Neoplasms ◽  
White Blood Cells ◽  
Reference Value ◽  
Control Group ◽  
Vascular Endothelial ◽  
Clinical Issue ◽  
Thrombotic Complications ◽  
Endothelial Growth Factor

Aim: The assessment of angiogenic parameters in so-called “liquid tumors”, such as myeloproliferative neoplasms, remains an open clinical issue. The aim of the study is to evaluate the concentration of vascular endothelial growth factor (VEGF-A) and soluble receptors sVEGFR-1 and sVEGFR-2 in relations to risk factors of thrombosis in patients with polycythemia vera (PV). Material/Methods: A total of 45 patients suffering from newly diagnosed PV and 30 healthy volunteers were enrolled into the study. Polycythemia vera was diagnosed according to the WHO (2008) criteria. In the citrated plasma samples VEGF-A, sVEGFR-1 and sVEGFR-2 were measured using ELISA tests. Results: VEGF-A concentration was three-fold higher and sVEGFR-2 significantly lower in PV patients as compared to the control group. VEGF-A concentration was significantly higher in PV patients with JAK2V617F mutation, as compared to patients without this mutation. SVEGFR-1 and sVEGFR-2 concentrations were similar in the analyzed subgroups. In PV patients with an increased number of white blood cells (WBCs), the above upper reference value (≥10 G/l), VEGF-A concentration was two-fold higher than in patients with WBCs number <10 G/l. However, sVEGFR-1 and sVEGFR-2 concentrations did not differ between the analyzed subgroups. Analysis of correlations revealed only one relation between VEGF-A and WBCs number. Conclusions: Increased VEGF-A and decreased sVEGFR-2 concentrations in polycythemia vera patients as compared to the control group indicate an intensification of the process of angiogenesis. A higher concentration of VEGF-A in PV patients with leukocytosis and a positive correlation between WBCs number and VEGF-A reflect the potential role of VEGF-A in the pathogenesis of thrombotic complications in hypercoagulable state in PV patients.

scholarly journals Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

2020 ◽  
Author(s):  
aida santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  
Keyword(s):  
Immune System ◽  
Educational Level ◽  
Blood Cells ◽  
Adaptive Response ◽  
White Blood Cells ◽  
Principal Component ◽  
Serum Markers ◽  
Response Component ◽  
Humoral Immune ◽  
Humoral Immune System

Abstract Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions.Methods: From the AMORIS cohort, 5,513 individuals were identified with baseline measurements of serum humoral immune (immunoglobulin G, A & M (IgG, IgA, IgM)) and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

Reference Values for Selected Blood Parameters in Rabbits: Effects of Age and Physiological Status

2019 ◽  
Author(s):  
M. J. Argente ◽  
D. M. Abad-Salazar ◽  
E. M. Bermejo-González ◽  
M. L. Garcíaz ◽  
A. López-Palazón
Keyword(s):  
Animal Model ◽  
Immune System ◽  
Health Status ◽  
Blood Cells ◽  
White Blood Cells ◽  
Blood Parameters ◽  
Physiological Status ◽  
Immune Challenge ◽  
Leukocyte Counts ◽  
Over Time

Rabbit is widely used as an experimental animal model in infectious and non-infectious diseases. The haematologic data can be helpful in evaluating the health status of animals over time. The aim of this study was to determine the levels of red blood cells (RBC), white blood cells (WBC) and differential leukocyte counts in 5 nulliparous and 5 multiparous females, i.e. in young and older animals, at mating and at delivery. The values of RBC did not change with age, but WBC and lymphocytes decreased with age, a -33% and a -60% less in multiparous females than nulliparous ones. Monocytes count was double at delivery than at mating. In conclusion, aging on the immune system is manifested as reduction in production of mature lymphocytes and as a result, older females would not respond to immune challenge as robustly as the young ones. Physiological status is only related to production of monocytes.

scholarly journals Electrodeformation of White Blood Cells Enriched with Gold Nanoparticles

2021 ◽  
Author(s):  
Nicholas G. Hallfors ◽  
Jeremy M. Teo ◽  
Peter Bertone ◽  
Chakra Joshi ◽  
Ajymurat Orozaliev ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Immune System ◽  
Blood Cells ◽  
Microelectrode Array ◽  
White Blood Cells ◽  
Valuable Insight ◽  
System Activity ◽  
Combined Use ◽  
Insight Into

The elasticity of white blood cells (WBCs) provides valuable insight into the condition of the cells themselves, the presence of some diseases, as well as immune system activity. In this work, we describe a novel process of refined control of WBCs elasticity through a combined use of gold nanoparticles (AuNPs) and the microelectrode array device. The capture and controlled deformation of gold nanoparticles enriched white blood cells in vitro are demonstrated and quantified. Gold nanoparticles enhance the effect of electrically induced deformation and make the DEP related processes more controllable.

scholarly journals Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Aida Santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  
Keyword(s):  
Immune System ◽  
Educational Level ◽  
Blood Cells ◽  
Adaptive Response ◽  
White Blood Cells ◽  
Principal Component ◽  
Serum Markers ◽  
Response Component ◽  
Humoral Immune ◽  
Humoral Immune System

Abstract Background Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral (antibody) immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors may influence these interactions. From the AMORIS cohort, 5513 individuals were identified with baseline measurements of serum humoral immune [immunoglobulin G, A & M (IgG, IgA, IgM)] and inflammation (C-reactive protein (CRP), albumin, haptoglobin, white blood cells (WBC), iron and total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age. Results Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation. Conclusions These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

scholarly journals Association between serum markers of the humoral immune system and inflammation in the Swedish AMORIS study

2020 ◽  
Author(s):  
aida santaolalla ◽  
Sam Sollie ◽  
Ali Rislan ◽  
Debra H. Josephs ◽  
Niklas Hammar ◽  
...  
Keyword(s):  
Immune System ◽  
Educational Level ◽  
Blood Cells ◽  
Adaptive Response ◽  
White Blood Cells ◽  
Principal Component ◽  
Serum Markers ◽  
Response Component ◽  
Humoral Immune ◽  
Humoral Immune System

Abstract Background: Although the onset of inflammatory cascades may profoundly influence the nature of antibody responses, the interplay between inflammatory and humoral immune markers remains unclear. Thus, we explored the reciprocity between the humoral immune system and inflammation and assessed how external socio-demographic factors influence these interactions.Methods: From the AMORIS cohort, 5,513 individuals were identified with baseline measurements of serum humoral immune (immunoglobulin G, A & M) and inflammation (CRP, albumin, haptoglobin, white blood cells, iron & total iron-binding capacity) markers measured on the same day. Correlation analysis, principal component analysis and hierarchical clustering were used to evaluate biomarkers correlation, variation and associations. Multivariate analysis of variance was used to assess associations between biomarkers and educational level, socio-economic status, sex and age.Results: Frequently used serum markers for inflammation, CRP, haptoglobin and white blood cells, correlated together. Markers of the humoral immune system, immunoglobulin A and G, also correlated together. Hierarchical clustering and principal component analysis confirmed the interaction between these main biological responses, showing an acute response component (CRP, Haptoglobin, WBC, IgM) and adaptive response component (Albumin, Iron, TIBC, IgA, IgG). A socioeconomic gradient associated with worse health outcomes was observed, specifically low educational level, older age and male sex were associated with serum levels that indicated infection and inflammation.Conclusions: These findings indicate that serum markers of the humoral immune system and inflammation closely interact in response to infection or inflammation. Correlation and clustering analysis presented two main immune response components: an acute and an adaptive response, comprising markers of both biological pathways. Future studies should shift from single internal marker assessment to multiple humoral and inflammation serum markers combined, when assessing risk of clinical outcomes such as cancer.

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