OSTEOPROTEGERIN (OPG) AND INTERLEUKIN-8 (IL-8) IMMUNOSTAINING IN BONE MARROW (BM) BIOPSIES OF PATIENTS WITH PH-NEGATIVE MYELOPROLIFERATIVE DISORDERS (MPD) AT DIAGNOSIS: CLINICAL CORRELATIONS
(Abstract release date: 05/19/16)
EHA Library. Triantafyllopoulou D. 06/09/16; 132895; E1346
Dr. Diana Triantafyllopoulou
Contributions
Contributions
Abstract
Abstract: E1346
Type: Eposter Presentation
Background
Both IL-8 and OPG have been implicated in the pathogenesis and clinical manifestations of myelofibrosis (MF), the most severe Ph(-) MPD. IL-8 and its receptors were reported to promote altered megakaryocyte (MGK) growth (Emadi et al), a typical MF finding, while OPG was found upregulated in endothelial cells (Bock et al).
Aims
To evaluate the expression and intensity of IL-8 and OPG immunostaining in BM biopsy of MPD patients at diagnosis and to study any eventual correlations between them and clinical characteristics or outcome.
Methods
78 patients were studied, diagnosed with MPN from 1984 to 2012 with a median follow up period of 55 months. Median age was 65 years, 49 were males. 22% were diagnosed with polycythemia vera (PV), 42% with essential thrombocytosis (ET) and 36% with MF. Of those, 58% had splenomegaly, 8% had bone pain, 81% presented with fatigue, 9% had sweating, 11.5% experienced a thrombotic event, 5% lost weight and 77% were JAK2 positive. Karyotype was abnormal in 32% while 7% presented unfavourable karyotype findings. Immunostaining for IL-8 and OPG was performed on paraffin-embedded 4μm sections of formalin fixed BM biopsies, carried out at the time of diagnosis, using the two-step peroxidase conjugated polymer technique. Grade of positivity and intensity of IL-8 and OPG expression was scored according to a 0 to 3 scale. Statistical analysis was performed conventionally, using the SPSS version 22.0 package, and p values <0.05 were considered significant.
Results
There was no significant difference observed concerning the grade of expression of both stainings among the different MPN-groups. High intensity of IL-8 expression in MGK correlated, in the whole cohort, with a high neutrophil count (p=0.029), low lymphocyte count (p=0.026), and increased haemoglobin (p=0.02). OPG was also expressed in cells of myeloid lineage (MLC) and its high intensity in MLC was observed in patients with high platelet counts (p=0.015). High intensity of OPG expression in MGK correlated with high neutrophil counts (p=0.045), high hemoglobin (p=0.045), high platelet counts (p=0.02), and a favourable karyotype (p=0.006). Most importantly, OPG low intensity in MGK correlated with poor survival (p=0.012). There was no correlation found between OPG and bone pain.
Conclusion
Our most important finding is that high intensity of OPG expression in MGK correlated with increased survival and a favourable karyotype in patients with MPDs (PV, ET and MF). To the best of our knowledge, this finding has not been reported yet. It should indeed be further validated. Refs:Emadi et al. IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis. Blood. 2005 Jan 15;105(2):464-73.Bock et al. Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with endothelial overexpression of osteoprotegerin. Br J Haematol. 2005 Jul;130(1):76-82.
Session topic: E-poster
Keyword(s): Hematopoietic microenvironment, IL-8, Immunohistochemistry, Marrow
Type: Eposter Presentation
Background
Both IL-8 and OPG have been implicated in the pathogenesis and clinical manifestations of myelofibrosis (MF), the most severe Ph(-) MPD. IL-8 and its receptors were reported to promote altered megakaryocyte (MGK) growth (Emadi et al), a typical MF finding, while OPG was found upregulated in endothelial cells (Bock et al).
Aims
To evaluate the expression and intensity of IL-8 and OPG immunostaining in BM biopsy of MPD patients at diagnosis and to study any eventual correlations between them and clinical characteristics or outcome.
Methods
78 patients were studied, diagnosed with MPN from 1984 to 2012 with a median follow up period of 55 months. Median age was 65 years, 49 were males. 22% were diagnosed with polycythemia vera (PV), 42% with essential thrombocytosis (ET) and 36% with MF. Of those, 58% had splenomegaly, 8% had bone pain, 81% presented with fatigue, 9% had sweating, 11.5% experienced a thrombotic event, 5% lost weight and 77% were JAK2 positive. Karyotype was abnormal in 32% while 7% presented unfavourable karyotype findings. Immunostaining for IL-8 and OPG was performed on paraffin-embedded 4μm sections of formalin fixed BM biopsies, carried out at the time of diagnosis, using the two-step peroxidase conjugated polymer technique. Grade of positivity and intensity of IL-8 and OPG expression was scored according to a 0 to 3 scale. Statistical analysis was performed conventionally, using the SPSS version 22.0 package, and p values <0.05 were considered significant.
Results
There was no significant difference observed concerning the grade of expression of both stainings among the different MPN-groups. High intensity of IL-8 expression in MGK correlated, in the whole cohort, with a high neutrophil count (p=0.029), low lymphocyte count (p=0.026), and increased haemoglobin (p=0.02). OPG was also expressed in cells of myeloid lineage (MLC) and its high intensity in MLC was observed in patients with high platelet counts (p=0.015). High intensity of OPG expression in MGK correlated with high neutrophil counts (p=0.045), high hemoglobin (p=0.045), high platelet counts (p=0.02), and a favourable karyotype (p=0.006). Most importantly, OPG low intensity in MGK correlated with poor survival (p=0.012). There was no correlation found between OPG and bone pain.
Conclusion
Our most important finding is that high intensity of OPG expression in MGK correlated with increased survival and a favourable karyotype in patients with MPDs (PV, ET and MF). To the best of our knowledge, this finding has not been reported yet. It should indeed be further validated. Refs:Emadi et al. IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis. Blood. 2005 Jan 15;105(2):464-73.Bock et al. Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with endothelial overexpression of osteoprotegerin. Br J Haematol. 2005 Jul;130(1):76-82.
Session topic: E-poster
Keyword(s): Hematopoietic microenvironment, IL-8, Immunohistochemistry, Marrow
Abstract: E1346
Type: Eposter Presentation
Background
Both IL-8 and OPG have been implicated in the pathogenesis and clinical manifestations of myelofibrosis (MF), the most severe Ph(-) MPD. IL-8 and its receptors were reported to promote altered megakaryocyte (MGK) growth (Emadi et al), a typical MF finding, while OPG was found upregulated in endothelial cells (Bock et al).
Aims
To evaluate the expression and intensity of IL-8 and OPG immunostaining in BM biopsy of MPD patients at diagnosis and to study any eventual correlations between them and clinical characteristics or outcome.
Methods
78 patients were studied, diagnosed with MPN from 1984 to 2012 with a median follow up period of 55 months. Median age was 65 years, 49 were males. 22% were diagnosed with polycythemia vera (PV), 42% with essential thrombocytosis (ET) and 36% with MF. Of those, 58% had splenomegaly, 8% had bone pain, 81% presented with fatigue, 9% had sweating, 11.5% experienced a thrombotic event, 5% lost weight and 77% were JAK2 positive. Karyotype was abnormal in 32% while 7% presented unfavourable karyotype findings. Immunostaining for IL-8 and OPG was performed on paraffin-embedded 4μm sections of formalin fixed BM biopsies, carried out at the time of diagnosis, using the two-step peroxidase conjugated polymer technique. Grade of positivity and intensity of IL-8 and OPG expression was scored according to a 0 to 3 scale. Statistical analysis was performed conventionally, using the SPSS version 22.0 package, and p values <0.05 were considered significant.
Results
There was no significant difference observed concerning the grade of expression of both stainings among the different MPN-groups. High intensity of IL-8 expression in MGK correlated, in the whole cohort, with a high neutrophil count (p=0.029), low lymphocyte count (p=0.026), and increased haemoglobin (p=0.02). OPG was also expressed in cells of myeloid lineage (MLC) and its high intensity in MLC was observed in patients with high platelet counts (p=0.015). High intensity of OPG expression in MGK correlated with high neutrophil counts (p=0.045), high hemoglobin (p=0.045), high platelet counts (p=0.02), and a favourable karyotype (p=0.006). Most importantly, OPG low intensity in MGK correlated with poor survival (p=0.012). There was no correlation found between OPG and bone pain.
Conclusion
Our most important finding is that high intensity of OPG expression in MGK correlated with increased survival and a favourable karyotype in patients with MPDs (PV, ET and MF). To the best of our knowledge, this finding has not been reported yet. It should indeed be further validated. Refs:Emadi et al. IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis. Blood. 2005 Jan 15;105(2):464-73.Bock et al. Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with endothelial overexpression of osteoprotegerin. Br J Haematol. 2005 Jul;130(1):76-82.
Session topic: E-poster
Keyword(s): Hematopoietic microenvironment, IL-8, Immunohistochemistry, Marrow
Type: Eposter Presentation
Background
Both IL-8 and OPG have been implicated in the pathogenesis and clinical manifestations of myelofibrosis (MF), the most severe Ph(-) MPD. IL-8 and its receptors were reported to promote altered megakaryocyte (MGK) growth (Emadi et al), a typical MF finding, while OPG was found upregulated in endothelial cells (Bock et al).
Aims
To evaluate the expression and intensity of IL-8 and OPG immunostaining in BM biopsy of MPD patients at diagnosis and to study any eventual correlations between them and clinical characteristics or outcome.
Methods
78 patients were studied, diagnosed with MPN from 1984 to 2012 with a median follow up period of 55 months. Median age was 65 years, 49 were males. 22% were diagnosed with polycythemia vera (PV), 42% with essential thrombocytosis (ET) and 36% with MF. Of those, 58% had splenomegaly, 8% had bone pain, 81% presented with fatigue, 9% had sweating, 11.5% experienced a thrombotic event, 5% lost weight and 77% were JAK2 positive. Karyotype was abnormal in 32% while 7% presented unfavourable karyotype findings. Immunostaining for IL-8 and OPG was performed on paraffin-embedded 4μm sections of formalin fixed BM biopsies, carried out at the time of diagnosis, using the two-step peroxidase conjugated polymer technique. Grade of positivity and intensity of IL-8 and OPG expression was scored according to a 0 to 3 scale. Statistical analysis was performed conventionally, using the SPSS version 22.0 package, and p values <0.05 were considered significant.
Results
There was no significant difference observed concerning the grade of expression of both stainings among the different MPN-groups. High intensity of IL-8 expression in MGK correlated, in the whole cohort, with a high neutrophil count (p=0.029), low lymphocyte count (p=0.026), and increased haemoglobin (p=0.02). OPG was also expressed in cells of myeloid lineage (MLC) and its high intensity in MLC was observed in patients with high platelet counts (p=0.015). High intensity of OPG expression in MGK correlated with high neutrophil counts (p=0.045), high hemoglobin (p=0.045), high platelet counts (p=0.02), and a favourable karyotype (p=0.006). Most importantly, OPG low intensity in MGK correlated with poor survival (p=0.012). There was no correlation found between OPG and bone pain.
Conclusion
Our most important finding is that high intensity of OPG expression in MGK correlated with increased survival and a favourable karyotype in patients with MPDs (PV, ET and MF). To the best of our knowledge, this finding has not been reported yet. It should indeed be further validated. Refs:Emadi et al. IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis. Blood. 2005 Jan 15;105(2):464-73.Bock et al. Osteosclerosis in advanced chronic idiopathic myelofibrosis is associated with endothelial overexpression of osteoprotegerin. Br J Haematol. 2005 Jul;130(1):76-82.
Session topic: E-poster
Keyword(s): Hematopoietic microenvironment, IL-8, Immunohistochemistry, Marrow
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