Contributions
Abstract: PB2301
Type: Publication Only
Background
The levels of different cytokines including VEGF, interleukin (IL) 6, IL-8 (CXCL8), and other molecules involved in inflammation were shown to be elevated in patients with primary myelofibrosis (PMF), a myeloproliferative neoplasm that still remains incurable without allogeneic hematopoietic stem cell transplantation. However, most of the studies give scarce data about clinical and genetic correlations with cytokine levels. So, the prognostic significance of cytokine concentrations is still unclear, especially under different palliative treatment strategies, including hydroxyurea and interferon-alpha, and in different populations.
Aims
To evaluate the plasma levels and clinical correlations of VEGF, IL-8, IL-6 and TNF-alpha and in patients with primary myelofibrosis from Ukraine.
Methods
The total of 45 patients clinically diagnosed with PMF were examined for plasma levels of VEGF, IL-8, IL-6 and TNF-alpha levels using ELISA on admission and after a year of follow-up. Control group consisted of 35 healthy persons. The study group included 21 patients with early PMF, the others had overt PMF according to WHO 2016 classification. Histological, cytogenetic and molecular genetic studies were performed for PMF patients. All the PMF patients received treatment with either hydroxyurea or interferon-alpha. Statistical differences were analyzed by the Mann-Whitney test.
Results
The upper quartile level of all studied cytokines in the group of patients with PMF exceeded the maximal levels of healthy donors. However, only VEGF and IL-8 levels of the patients from the study group were significantly increased (p=0.016 and p=0.044 respectively) comparing to the controls. Moreover, the levels of VEGF and IL-8 were higher than maximal for control group in only 37.8% and 46.7% of the patients with PMF. There were no differences found in the levels of the cytokines in patients with and without JAK2V617F mutation, but the TNF-alpha levels were significantly increased (p=0.001) in the patients bearing either MPL515L or MPL515K mutations. The level of IL-8 was significantly higher (p=0.048) in patients with cytogenetic abnormalities. There were no statistically significant differences in the cytokine levels between early and overt PMF groups. The levels of the cytokines had no significant differences between Dynamic International Prognostic Scoring System Plus risk groups. However, all 5 patients that died during the follow-up had significantly higher level of both IL-8 (p=0.0004) and IL-6 (p=0.02). The VEGF level was decreased at the follow-up on either hydroxyurea or interferon-alpha treatment in 93.3% of patients respectively, and the TNF-alpha levels increased in 88.9% of the patients, even if they were within the control group range at presentation. At the same time the IL-8 and IL-6 levels were not significantly changed under the same treatment during the follow-up.
Conclusion
The levels of VEGF and IL-8 may be increased in some patients with PMF, but this is not a disease specific feature, because most of the patients have the level of the cytokines within the range of values observed in healthy individuals. It is possible that the treatment with hydroxyurea and interferon-alpha could change the levels of VEGF and TNF-alpha, however the IL-8 and IL-6 levels do not change significantly after the year of follow-up on the same therapy and may be related with inferior prognosis. As the higher IL-8 level correlates with the presence of cytogenetic abnormalities, it is possible to suppose that cytogenetically abnormal cells may cause more intensive production of this cytokine.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): IL-6, IL-8, Myelofibrosis, VEGF
Abstract: PB2301
Type: Publication Only
Background
The levels of different cytokines including VEGF, interleukin (IL) 6, IL-8 (CXCL8), and other molecules involved in inflammation were shown to be elevated in patients with primary myelofibrosis (PMF), a myeloproliferative neoplasm that still remains incurable without allogeneic hematopoietic stem cell transplantation. However, most of the studies give scarce data about clinical and genetic correlations with cytokine levels. So, the prognostic significance of cytokine concentrations is still unclear, especially under different palliative treatment strategies, including hydroxyurea and interferon-alpha, and in different populations.
Aims
To evaluate the plasma levels and clinical correlations of VEGF, IL-8, IL-6 and TNF-alpha and in patients with primary myelofibrosis from Ukraine.
Methods
The total of 45 patients clinically diagnosed with PMF were examined for plasma levels of VEGF, IL-8, IL-6 and TNF-alpha levels using ELISA on admission and after a year of follow-up. Control group consisted of 35 healthy persons. The study group included 21 patients with early PMF, the others had overt PMF according to WHO 2016 classification. Histological, cytogenetic and molecular genetic studies were performed for PMF patients. All the PMF patients received treatment with either hydroxyurea or interferon-alpha. Statistical differences were analyzed by the Mann-Whitney test.
Results
The upper quartile level of all studied cytokines in the group of patients with PMF exceeded the maximal levels of healthy donors. However, only VEGF and IL-8 levels of the patients from the study group were significantly increased (p=0.016 and p=0.044 respectively) comparing to the controls. Moreover, the levels of VEGF and IL-8 were higher than maximal for control group in only 37.8% and 46.7% of the patients with PMF. There were no differences found in the levels of the cytokines in patients with and without JAK2V617F mutation, but the TNF-alpha levels were significantly increased (p=0.001) in the patients bearing either MPL515L or MPL515K mutations. The level of IL-8 was significantly higher (p=0.048) in patients with cytogenetic abnormalities. There were no statistically significant differences in the cytokine levels between early and overt PMF groups. The levels of the cytokines had no significant differences between Dynamic International Prognostic Scoring System Plus risk groups. However, all 5 patients that died during the follow-up had significantly higher level of both IL-8 (p=0.0004) and IL-6 (p=0.02). The VEGF level was decreased at the follow-up on either hydroxyurea or interferon-alpha treatment in 93.3% of patients respectively, and the TNF-alpha levels increased in 88.9% of the patients, even if they were within the control group range at presentation. At the same time the IL-8 and IL-6 levels were not significantly changed under the same treatment during the follow-up.
Conclusion
The levels of VEGF and IL-8 may be increased in some patients with PMF, but this is not a disease specific feature, because most of the patients have the level of the cytokines within the range of values observed in healthy individuals. It is possible that the treatment with hydroxyurea and interferon-alpha could change the levels of VEGF and TNF-alpha, however the IL-8 and IL-6 levels do not change significantly after the year of follow-up on the same therapy and may be related with inferior prognosis. As the higher IL-8 level correlates with the presence of cytogenetic abnormalities, it is possible to suppose that cytogenetically abnormal cells may cause more intensive production of this cytokine.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): IL-6, IL-8, Myelofibrosis, VEGF