SERUM LEVELS OF CYTOKINES AND SOLUBLE ADHESION MOLECULES IN ACTIVE ACUTE MYELOID LEUKEMIA AND COMPLETE REMISSION: EVIDENCE OF ENDOTHELIAL CELL ACTIVATION.
(Abstract release date: 05/19/16)
EHA Library. M Horacek J. 06/09/16; 134547; PB1647
Assoc. Prof. Jan M Horacek
Contributions
Contributions
Abstract
Abstract: PB1647
Type: Publication Only
Background
Acue myeloid leukemia cell are highly resistant to therapy. The presumed molecular basis of this resistance is the effect Tumor Necrosis Factor-α (TNF-α) and other cytokines on endothelial adhesion molecule expression.
Aims
The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules are involved in endothelial cell activation in acute myeloid leukemia (AML).
Methods
A total of 84 AML patients were studied. Two subgroups comprising 84 samples collected in active disease and 45 samples collected at AML complete remission (CR) were evaluated. Samples obtained after allogeneic stem cell transplantation were not included.We evaluated serum levels of the following 29 analytes: interleukins (IL-1α,IL-1β,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-15), Epidermal Growth Factor (EGF), GM-CSF, IFN-γ, Macrophage Inflammatory Protein-1α (MIP-1α), Monocyte Chemotactic Protein-1 (MCP-1), TNF-α, Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Matrix Metalloproteinase-9, soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Probability values (P)<0.05 were considered significant.
Results
In active disease, the levels of VCAM-1 correlated with ICAM-1 (P˂0.0001), E-SEL (P=0.0011), leukocyte count (P=0.0006), TNF-α (P˂0.0001), TNFR-2 (P˂0.0001), TNFR-1 (P=0.0047), LDH (P˂0.0001), IL-2Rα (P=0.0224) and IL-6R (P=0.0240). The ICAM-1 levels correlated with E-SEL (P=0.0285), TNFR-1 (P=0.0007), LDH (P=0.0344) and IL-6 (P=0.0646). E-SEL correlated with P-SEL (P˂0.0001), leukocyte count (P˂0.0001), LDH (P˂0.0001), TNFR-1 (P=0.0152), TNFR-2 (P=0.0202). CRP levels correlated with IL-6 (P˂0.0001), ICAM-1 (P=0.0122) and negatively with albumin levels (P=0.0175). The platelet count correlated with IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF. There was no correlation of age or haemaglobin levels with any evaluated analyte. In CR the levels of IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF (P˂0.0001) were higher, which was related to normalized platelet count. The levels of IL-6 were lower in CR with no significant correlation with CRP levels. The levels of VCAM-1, ICAM-1, E-SEL and P-SEL were decreased compared to active disease, which was not significant after Bonferroni correction of P. The P-SEL correlated with platelet count (P˂0.0001) and IL-8 (P˂0.0001), which was not observed in active disease. VCAM-1 correlated with ICAM-1 (P=0.0027), but not with E-SEL or P-SEL. The E-SEL did not correlate with P-SEL.
Conclusion
Our findings are in agreement with the results of studies showing that cytokine and chemokine expression are largely independent of variables, such as age, gender and haemoglobin levels. In active disease the adhesion molecule levels are influenced as a whole and correlate with leukocyte count, LDH and levels of TNF-α, TNFR-1 and TNFR-2. Understanding the relationship of evaluated analytes in active AML and CR is more important than simple comparison of their levels. Endothelial cells can release both E-SEL and P-SEL. This happens in active disease, where the correlation of E-SEL and leukocyte count is significant. In CR there was no significant correlation of E-SEL with P-SEL or leukocyte count. Platelets release only P-SEL and are the major source of P-SEL in CR. We interprete these data as direct evidence of endothelial cell activation in active AML.The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: E-poster
Keyword(s): Adhesion, AML, Cytokine, Endothelial cell
Type: Publication Only
Background
Acue myeloid leukemia cell are highly resistant to therapy. The presumed molecular basis of this resistance is the effect Tumor Necrosis Factor-α (TNF-α) and other cytokines on endothelial adhesion molecule expression.
Aims
The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules are involved in endothelial cell activation in acute myeloid leukemia (AML).
Methods
A total of 84 AML patients were studied. Two subgroups comprising 84 samples collected in active disease and 45 samples collected at AML complete remission (CR) were evaluated. Samples obtained after allogeneic stem cell transplantation were not included.We evaluated serum levels of the following 29 analytes: interleukins (IL-1α,IL-1β,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-15), Epidermal Growth Factor (EGF), GM-CSF, IFN-γ, Macrophage Inflammatory Protein-1α (MIP-1α), Monocyte Chemotactic Protein-1 (MCP-1), TNF-α, Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Matrix Metalloproteinase-9, soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Probability values (P)<0.05 were considered significant.
Results
In active disease, the levels of VCAM-1 correlated with ICAM-1 (P˂0.0001), E-SEL (P=0.0011), leukocyte count (P=0.0006), TNF-α (P˂0.0001), TNFR-2 (P˂0.0001), TNFR-1 (P=0.0047), LDH (P˂0.0001), IL-2Rα (P=0.0224) and IL-6R (P=0.0240). The ICAM-1 levels correlated with E-SEL (P=0.0285), TNFR-1 (P=0.0007), LDH (P=0.0344) and IL-6 (P=0.0646). E-SEL correlated with P-SEL (P˂0.0001), leukocyte count (P˂0.0001), LDH (P˂0.0001), TNFR-1 (P=0.0152), TNFR-2 (P=0.0202). CRP levels correlated with IL-6 (P˂0.0001), ICAM-1 (P=0.0122) and negatively with albumin levels (P=0.0175). The platelet count correlated with IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF. There was no correlation of age or haemaglobin levels with any evaluated analyte. In CR the levels of IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF (P˂0.0001) were higher, which was related to normalized platelet count. The levels of IL-6 were lower in CR with no significant correlation with CRP levels. The levels of VCAM-1, ICAM-1, E-SEL and P-SEL were decreased compared to active disease, which was not significant after Bonferroni correction of P. The P-SEL correlated with platelet count (P˂0.0001) and IL-8 (P˂0.0001), which was not observed in active disease. VCAM-1 correlated with ICAM-1 (P=0.0027), but not with E-SEL or P-SEL. The E-SEL did not correlate with P-SEL.
Conclusion
Our findings are in agreement with the results of studies showing that cytokine and chemokine expression are largely independent of variables, such as age, gender and haemoglobin levels. In active disease the adhesion molecule levels are influenced as a whole and correlate with leukocyte count, LDH and levels of TNF-α, TNFR-1 and TNFR-2. Understanding the relationship of evaluated analytes in active AML and CR is more important than simple comparison of their levels. Endothelial cells can release both E-SEL and P-SEL. This happens in active disease, where the correlation of E-SEL and leukocyte count is significant. In CR there was no significant correlation of E-SEL with P-SEL or leukocyte count. Platelets release only P-SEL and are the major source of P-SEL in CR. We interprete these data as direct evidence of endothelial cell activation in active AML.The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: E-poster
Keyword(s): Adhesion, AML, Cytokine, Endothelial cell
Abstract: PB1647
Type: Publication Only
Background
Acue myeloid leukemia cell are highly resistant to therapy. The presumed molecular basis of this resistance is the effect Tumor Necrosis Factor-α (TNF-α) and other cytokines on endothelial adhesion molecule expression.
Aims
The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules are involved in endothelial cell activation in acute myeloid leukemia (AML).
Methods
A total of 84 AML patients were studied. Two subgroups comprising 84 samples collected in active disease and 45 samples collected at AML complete remission (CR) were evaluated. Samples obtained after allogeneic stem cell transplantation were not included.We evaluated serum levels of the following 29 analytes: interleukins (IL-1α,IL-1β,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-15), Epidermal Growth Factor (EGF), GM-CSF, IFN-γ, Macrophage Inflammatory Protein-1α (MIP-1α), Monocyte Chemotactic Protein-1 (MCP-1), TNF-α, Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Matrix Metalloproteinase-9, soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Probability values (P)<0.05 were considered significant.
Results
In active disease, the levels of VCAM-1 correlated with ICAM-1 (P˂0.0001), E-SEL (P=0.0011), leukocyte count (P=0.0006), TNF-α (P˂0.0001), TNFR-2 (P˂0.0001), TNFR-1 (P=0.0047), LDH (P˂0.0001), IL-2Rα (P=0.0224) and IL-6R (P=0.0240). The ICAM-1 levels correlated with E-SEL (P=0.0285), TNFR-1 (P=0.0007), LDH (P=0.0344) and IL-6 (P=0.0646). E-SEL correlated with P-SEL (P˂0.0001), leukocyte count (P˂0.0001), LDH (P˂0.0001), TNFR-1 (P=0.0152), TNFR-2 (P=0.0202). CRP levels correlated with IL-6 (P˂0.0001), ICAM-1 (P=0.0122) and negatively with albumin levels (P=0.0175). The platelet count correlated with IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF. There was no correlation of age or haemaglobin levels with any evaluated analyte. In CR the levels of IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF (P˂0.0001) were higher, which was related to normalized platelet count. The levels of IL-6 were lower in CR with no significant correlation with CRP levels. The levels of VCAM-1, ICAM-1, E-SEL and P-SEL were decreased compared to active disease, which was not significant after Bonferroni correction of P. The P-SEL correlated with platelet count (P˂0.0001) and IL-8 (P˂0.0001), which was not observed in active disease. VCAM-1 correlated with ICAM-1 (P=0.0027), but not with E-SEL or P-SEL. The E-SEL did not correlate with P-SEL.
Conclusion
Our findings are in agreement with the results of studies showing that cytokine and chemokine expression are largely independent of variables, such as age, gender and haemoglobin levels. In active disease the adhesion molecule levels are influenced as a whole and correlate with leukocyte count, LDH and levels of TNF-α, TNFR-1 and TNFR-2. Understanding the relationship of evaluated analytes in active AML and CR is more important than simple comparison of their levels. Endothelial cells can release both E-SEL and P-SEL. This happens in active disease, where the correlation of E-SEL and leukocyte count is significant. In CR there was no significant correlation of E-SEL with P-SEL or leukocyte count. Platelets release only P-SEL and are the major source of P-SEL in CR. We interprete these data as direct evidence of endothelial cell activation in active AML.The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: E-poster
Keyword(s): Adhesion, AML, Cytokine, Endothelial cell
Type: Publication Only
Background
Acue myeloid leukemia cell are highly resistant to therapy. The presumed molecular basis of this resistance is the effect Tumor Necrosis Factor-α (TNF-α) and other cytokines on endothelial adhesion molecule expression.
Aims
The aim of this study was to test the hypothesis that cytokines and soluble adhesion molecules are involved in endothelial cell activation in acute myeloid leukemia (AML).
Methods
A total of 84 AML patients were studied. Two subgroups comprising 84 samples collected in active disease and 45 samples collected at AML complete remission (CR) were evaluated. Samples obtained after allogeneic stem cell transplantation were not included.We evaluated serum levels of the following 29 analytes: interleukins (IL-1α,IL-1β,IL-2,IL-3,IL-4,IL-5,IL-6,IL-7,IL-8,IL-10,IL-12,IL-13,IL-15), Epidermal Growth Factor (EGF), GM-CSF, IFN-γ, Macrophage Inflammatory Protein-1α (MIP-1α), Monocyte Chemotactic Protein-1 (MCP-1), TNF-α, Vascular Endothelial Growth Factor (VEGF), E-selectin (E-SEL), P-selectin (P-SEL), Intercellular Adhesion Molecule-1 (ICAM-1), Vascular Cell Adhesion Molecule-1 (VCAM-1), Matrix Metalloproteinase-9, soluble IL-2 receptor-α (sIL-2Rα) and soluble receptors for IL-6 (sIL-6R) and TNF-α type I and II (TNFR-1,2). All biomarkers were measured by biochip array technology on Evidence Investigator analyzer (Randox). Probability values (P)<0.05 were considered significant.
Results
In active disease, the levels of VCAM-1 correlated with ICAM-1 (P˂0.0001), E-SEL (P=0.0011), leukocyte count (P=0.0006), TNF-α (P˂0.0001), TNFR-2 (P˂0.0001), TNFR-1 (P=0.0047), LDH (P˂0.0001), IL-2Rα (P=0.0224) and IL-6R (P=0.0240). The ICAM-1 levels correlated with E-SEL (P=0.0285), TNFR-1 (P=0.0007), LDH (P=0.0344) and IL-6 (P=0.0646). E-SEL correlated with P-SEL (P˂0.0001), leukocyte count (P˂0.0001), LDH (P˂0.0001), TNFR-1 (P=0.0152), TNFR-2 (P=0.0202). CRP levels correlated with IL-6 (P˂0.0001), ICAM-1 (P=0.0122) and negatively with albumin levels (P=0.0175). The platelet count correlated with IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF. There was no correlation of age or haemaglobin levels with any evaluated analyte. In CR the levels of IL-7 (P˂0.0001), EGF (P˂0.0001) and VEGF (P˂0.0001) were higher, which was related to normalized platelet count. The levels of IL-6 were lower in CR with no significant correlation with CRP levels. The levels of VCAM-1, ICAM-1, E-SEL and P-SEL were decreased compared to active disease, which was not significant after Bonferroni correction of P. The P-SEL correlated with platelet count (P˂0.0001) and IL-8 (P˂0.0001), which was not observed in active disease. VCAM-1 correlated with ICAM-1 (P=0.0027), but not with E-SEL or P-SEL. The E-SEL did not correlate with P-SEL.
Conclusion
Our findings are in agreement with the results of studies showing that cytokine and chemokine expression are largely independent of variables, such as age, gender and haemoglobin levels. In active disease the adhesion molecule levels are influenced as a whole and correlate with leukocyte count, LDH and levels of TNF-α, TNFR-1 and TNFR-2. Understanding the relationship of evaluated analytes in active AML and CR is more important than simple comparison of their levels. Endothelial cells can release both E-SEL and P-SEL. This happens in active disease, where the correlation of E-SEL and leukocyte count is significant. In CR there was no significant correlation of E-SEL with P-SEL or leukocyte count. Platelets release only P-SEL and are the major source of P-SEL in CR. We interprete these data as direct evidence of endothelial cell activation in active AML.The work was supported by a long-term organisation development plan 1011 (FMHS).
Session topic: E-poster
Keyword(s): Adhesion, AML, Cytokine, Endothelial cell
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