The Relationship Of Notch And Ang/Tie2 Signaling Pathways In The Angiogenesis Of Acute Myeloid Leukemia Patients

BackgroundAcute myeloid leukemia (AML) is a serious type of hematological malignancies that jeopardizes the health of AML patients. Angiogenesis is defined as a highly ordered neoformation of capillaries from preexisting blood vessels, which is not only required for growth, progression, and metastasis of solid tumors but also plays a crucial role in hematologic malignancies. Especially for the rapid progression and poor prognosis of AML. For the past few years, it is indicated that Notch and Ang/Tie2 signaling pathways participate tumor angiogenesis. Recently it is reported that the expression of Ang/Tie2 signaling pathway related genes are regulated by Notch1 gene in vascular endothelial cells. But whether the relationships exist in tumor cells are currently not defined. Aberrant expressions of Notch and Ang/Tie2 signalings have been found in bone marrow microenvironment of acute leukemia. The expression of Ang/Tie2 signaling pathway related genes has been reported in AML, but the results of different research groups are not the same. Despite extensive studies on Ang/Tie2 signaling pathway in AML, the role of Notch and its relationship with Ang/Tie2 in modulating AML angiogenesis are unknown.ObjectivesIn the present study, we examine the mRNA level of Notch1, Ang-1, Ang-2 and Tie2 in peripheral blood mononuclear cells (PBMCs) of patients with de novo AML to investigate the roles and relationship Notch and Ang/Tie2 signaling pathways in AML angiogenesis and discuss possible mechanism of the two pathways in AML angiogenesis.Methods1. Patients and controls: We selected 40 healthy volunteers (normal control) and 40 patients with newly diagnosed de novo AML.2. We established real-time quantitative RT-PCR (real-time Q-RT- PCR) methods to testify the expression of Notch1, Ang-1, Ang-2 and Tie2 in PBMCs of patients with AML and GAPDH was selected as internal control.3. Variables were assessed by the Wilcoxon rank-sum test and Spearman rank correlation.Results1. The expression levels of Notch1 and Ang-2 in AML patients were higher than those in normal controls, the difference of Ang-1 and Tie2 were not significant.2. Notch1 exhibited a positive correlation with Ang-2 in AML patients, but not in normal controls.Conclusions1. Notch signaling pathway is activated in AML depending on the up-regulation of Notch1.2. Ang/Tie2 signaling pathway is activated in AML mainly depending on the up-regulation of Ang-2.3. The coaction and correlation of Notch and Ang/Tie2 signaling pathways all modulated the angiogenesis in bone marrow microenvironment of AML.