الفهرس 
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Abstract
Angiogenesis play a critical role in the development and growth of solid tumors as well as hematological malignancies. The prognostic impact of angiogenic growth factors in hematological malignancies has gained significant attention over the past few years. Angiopoietin-2 (Ang-2) is the naturally occurring antagonist to Angiopoietin-1 (Ang-1) both being among angiogenic growth factors involved in either vascular stabilization or cellular proliferation.
Recent studies have demonstrated the over-expression and prognostic significance of cellular Ang-2 expression in AML BM and isolated peripheral AML blasts. However, no enough data are available on blood levels of Ang-2 in AML.
The aim of the present study was to estimate the level of circulating Anigopoietin-2 in AML and to determine its prognostic relevance in AML patients. It was performed on 40 newly diagnosed AML patients attending the Hematology Oncology Clinic of Ain Shams University Hospital, including 22 males (55%) and 18 females (45%) with age ranging from 15 to 78 years with a mean value of 42.2±15.2 years and 20 healthy subjects with non hematological malignancy were taken as control, including 11 males (55%) and 9 females (45%) with age ranging from 17 to 53 years with a mean value of 36.9±11.1 years.
All the patients were subjected to full history taking, full clinical examination and routine laboratory investigations. Bone marrow examination, with morphological assessment of bone marrow blast cell percentage, routine immunopheno-typing and conventional cytogenetic analysis were done (for study group only). Enzyme-linked immunosorbent assay (ELISA) for Ang-2 was performed on serum samples collected from both groups using RayBio® Human Angiopoietin-2 ELISA kit.
The results showed a higher mean value of Ang2 among males (3045.8±835.4) than females (2492.8±814.4) and this difference was of a statistical significance (p=0.04). However, we observed no statistical association between Ang2 levels and different age groups.
Regarding laboratory data, our study reported insignificant correlation between circulating levels of Ang2 and each of WBC count, hemoglobin level, platelet count, peripheral blood blasts and bone marrow blast infiltration.
Regarding cytogenetic analysis, no significant association was found between circulating Ang2 levels and cytogenetic abnormalities laying stress on t(8;21), t(15;17) and inv 16 (p > 0.05). Another finding was the lack of association between circulating Ang2 levels and different FAB subtypes (p = 0.366).
The results revealed that the mean value of Ang2 was 2797±861.7 pg/ml among the study group compared to a lower mean value of 805.2±379.1 pg/ml among the control group and this difference was statistically highly significant (p = 0.001).
Moreover, our results demonstrated a strong correlation between circulating levels of Ang2 and overall survival in treated AML patients with induction treatment. Patients with high plasma levels of Ang2 (3125.4±773.8) displayed a significantly worse overall survival than those with lower levels (2187.1±678.1) and this difference was statistically highly significant (p = 0.001).
The best cut off value for Ang2 in predicting those patients with poor prognosis was found to be 2579 pg/ml
(p = 0.001) with sensitivity 73.1% and specificity 71.1%.
In summary, the results of our study clearly demonstrate the independent prognostic significance of circulating Ang2 in AML. A better understanding of the precise functions of angiopoietin signaling pathways in AML may open new avenues for therapeutic interventions. If confirmed in large AML trials, measurement of Ang2 concentration at disease presentation may eventually find its way into clinical routine as an additional prognostic tool in the risk –stratified management of AML.