الفهرس 
Review of LiteratureOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemia is a life threatening problem with overall disease free survival below 80 %. Accumulating evidences suggest the role of angiogenesis in pathogenesis and progression of acute myeloid leukemia (Aguayo et al 1999). Angiogenesis is controlled by a balance between positive and negative angiogenic factors. Among the inhibitors of angiogenesis is endostatin. Endostatin is the most broad spectrum and least toxic angiogenesis inhibitor. It inhibits 65 different tumor types ( Folkman, 2005). The level of endosatin in acute myeloid leukemia and its relation to patient outcome; are up till now is controversial. The present study was carried out on 30 patients with acute myeloid leukemia (12 males and 18 females) besides 10 healthy normal persons as a control group. According to the clinical assessment, laboratory investigations, morphological FAB classification, immunophenotyping and cytochemical reactions, the patients group was classified into the following groups: Group I:This group comprised 30 patient recently diagnosed as acute myeloid leukemia before induction of chemotherapy (virgin cases). Virgin cases were followed up after chemotherapy and blood samples were taken after remission to form group II. Group II: This group comprised 25 patients with acute myeloid leukemia in remission (after 30 days of starting the induction chemotherapy ) were followed up for 12 months later. The number of patients at the end of 12 month was 6 patients and 19 died during this period. Control group: This group comprised 10 normal healthy persons of matched age and sex as control group. They were 4 males and 6 females, their ages ranged from 19 to 55 years. They were subjected to the same assay of the serum endostatin levels. The patients were subjected to the following: 1-Thorough history taking and clinical examinations: Including name, age, sex, complaints, general and local examination were done for detection of constitutional manifestations of leukemia including pallor, fever, purpura, any hemorrhagic manifestation in addition to presence of organomegally or lymphadenopathy. 2-Laboratory investigations: Complete blood count (CBC). BM aspiration. Cytochemical staining. Immunophenotyping analysis. Liver function tests including serum albumin, serum bilirubin, (SGOT), (SGPT). Serum creatinine. Serum uric acid 3- Assay of serum endostatin levels . The results of the present study are: In this present study the endostatin levels were compared in pre-treatment , post-treatment and in control groups: Serum levels of endostatin in the untreated AML patients befor induction chemotherapy were insignificantly high compared to that in healthy controls. Furthermore endostatin levels express more elevation after induction chemotherapy. There was no statistically significant difference in the endostatin level between the cases pre-treatment and controls (P=0.257). Regarding post-treatment endostatin level in the current study, it was significantly higher than the levels in pre-treatment and controls (P=0.001 and 0.000 respectively). Endostatin levels at time of diagnosis were compared in died, survived and control groups, showing marked incresae of serum endostatin level in survived group more than died and control groups, also it show no significant difference between died and control groups. Overall survival in relation to some AML risk factors: Peripheral WBCs count, platelet count , blast cells percentage in bone marrow , lymph node groups, FAB classification , hepatomegally and splenomegally most of them showed no significant relation, except for hepatomegally that had important relation to patients survival (P value=0.01). Overall survival in relation to pre-treatment endostatin level:According to the pre-treatment serum level, patients were divided into high (above 75th percentile) and low (below 75th percentile) groups using 75th percentile level as cutoff value. High serum endostatin patients survived for a significantly longer time than low serum endostatin patients (P=0.02). Using Cox proportional hazard regression model, the endostatin level was a statistically significant predictor of overall survival (P= 0.04), revealing that high level of endostatin is associated with long survival time. Based on current data, serum endostatin level is a prognostic factor for AML, and high serum endostatin levels correlate with good clinical outcome. The predictive value of serum endostatin levels appears to be independent of several known prognostic value. The mechanism underlying the association between the clinical outcome and serum endostatin level is unclear. This finding raises the possibility that endostatin may be used in AML therapy. Conclusions: Angiogenesis plays an important role in pathogenesis and progression of acute myeloid leukemia. Angiogenesis is controlled by a balance between positive and negative angiogenic factors. Among the inhibitors of angiogenesis is endostatin. Results of the current study show a marked incresae of serum endostatin level in survived group (lived more than 12 months) more than died and control groups. The endostatin level was a statistically significant predictor of overall survival (P=0 .04). Elevated endostatin levels at AML diagnosis is a good prognostic marker for patients’ outcome. Recommendations: According to the role of endostatin as inhibitor of angiogenic process and the role of angiogenesis in pathogenesis, proliferation and progression of acute leukemia, antiangiogenic agents should be used in treatment of acute leukemia alone or in combination with standard chemotherapy to improve the curance rate and to overcome refractory and relapsed problems. Wide scale study is recommended in order to validate these findings.