الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Acute myeloid leukemias (AMLs) are neoplastic proliferations arising in hematopoietic precursor cells in the bone marrow. They result in overgrowth of myeloblasts and other cells of myeloid lineage. The malignant cells replace the normal bone marrow cells, circulate in the blood, and may accumulate in other tissues, including the lymph nodes, liver, and spleen. 80-90% of leukemia in adults is AML. The Notch-1 receptor is a type I transmembrane protein. Interactions between Notch-1 and its ligands Jagged-1 and Dll-1 result in proteolytic cleavages within the receptor, and finally the intracellular domain (Notch-1-IC) is released and translocated in the nucleus. Notch-1 expression was also detected in CD34+ marrow progenitors and other cells in both the bone marrow and the peripheral blood. Jagged-1 and Deltalike1 (Dll-1) seem to be functionally opposite members of the Notch-1 ligand family, but the exact mechanisms of their function in AML remain unclear. The aim of this study was to evaluate the clinical role of Notch-1-IC and its ligands in newly diagnosed adult patients with AML. Expression of the Notch-1 intracellular domain and surface expression of Jagged-1 and Dll-1 ligands were assessed in leukemic blasts of newly diagnosed patients with AML by flow cytometry. Additionally, the expression of examined proteins was correlated with clinical data, laboratory data, FAB classification of AML, response to treatment and overall survival (OS). Fifty newly diagnosed adult AML patients were enrolled in this study. Most of them were presented with bleeding tendency (88%) and infectious manifestations (76%) and were classified as M2 (26%) or M5 (32%) according to FAB classification. The mean OS and DFS were 6.8 and 3.6 months, respectively. Notch-1 was positively expressed in 20% of studied patients. Positive Notch- 1 expression was associated with shorter OS (6.1 months) and DFS (3.1 months). Higher Notch-1 expression levels were significantly associated with lower CR and higher relapse rates. In contrary, Jagged-1 protein marker weas positively expressed in 56% studied patients, those patients showed shorter OS (6.6 months) and longer disease-free survival rates (3.6 months) compared to negatively expressed ones. Higher Jagged-1 expression levels were significantly associated with higher CR and lower relapse rates. Positive Dll-1 expression was recorded in 30 % patients, yet with no significant relationship with OS and DFS rates as well as clinical outcome after therapy. We can conclude that both Notch-1 receptor and its ligands, Jagged-1 and Dll-1, seem to be involved in AML pathogenesis, but mainly Jagged-1 and to lesser extent Dll-1 exerts an influence on clinical outcome. High Jagged-1 surface expression is associated with favorable prognosis in patients with AML. However, further studies are necessary to gain a better understanding of Notch-1 and its ligands mechanisms of action in AML.