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The Significance of Expression Angs/Tie-2 System in Leukemia

Author: ChengZhiYong
Tutor: DongZuoRen;Pan
School: Hebei Medical University
Course: Internal Medicine
Keywords: Leukemia Angiopoietins(Angs) Tie-2 Vascular endothelial growth factor (VEGF) RT-PCR Proliferation Indice (PI) Flow Cytometry (FCM)
CLC: R733.7
Type: Master's thesis
Year: 2004
Downloads: 62
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Abstract


Objective: Angiopoietins belong to a novel family of endothelial growth factors. They are newly certified and different from vascular endothelial growth factor (VEGF). Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) exist mainly at the surface of vascular endothelial cells. They function as ligands for the endothelial-specific receptor tyrosine kinase (Tie-2). Ang-1 and Ang-2 have an important role in the Angiogenesis: embryonic blood vessel development, remodeling of the vascular network, repairing in trauma and neovascularization. They are especially highly expressed in various human solid tumors and also have synergistic effect with VEGF on the induction of angiogenesis in tumor and affect tumor growing and metastasis . It has important significance for estimating the prognosis with Angs/Tie-2 system. Some foreign researchers have shown that angiopoietins and their receptor are abnormally expressed in fresh leukemia cells and leukemia cell lines. Angs/ Tie-2 with VEGF co-operat each other by autocrine and paracrine to participate in the occurrence and progression of leukemia. Therefore, the objective of the present study is to detect the expression of Angs/Tie-2 and VEGF mRNA in <WP=8>leukemia cell lines and fresh leukemia cells from patients with different subtype leukemia, to estimate whether Angs/ Tie-2 can co-operate with VEGF in leukemia genesis and progression.Methods: Heparinized bone marrow mononuclear cells (BMMNCs) were obtained with informed consent from adult patients with acute de novo myeloid leukemia (AML, n=50), recurrent AML (n=15), acute de novo lymphoblastic leukemia (ALL, n=10), chronic myelogenous leukemia (CML , n=15, among them, twelve patients in chronic phase, three in blast crises), adult AML patients in complete remission (CR) condition (AML-CR, n=15) and normal control (CN, n=15). The diagnosis was made according to the French, American and British (FAB) classification. All patients were classified into de novo group (AML, CML, ALL), recurrent group and normal control group. The expression of Ang-1, Ang-2, Tie-2 and VEGF mRNA in bone marrow mononuclear cells (BMNCs) from all subjects and in myeloid cell lines were measured by RT-PCR. The Proliferation Indices (PI) were also checked by flow cytometry (FCM). The relations among Ang-1, Ang-2, Tie-2, and VEGF mRNA expression level and patients’ prognosis in these three groups were analyzed respectively; the relations between Ang-1,Ang-2,Tie-2 and PI were also analyzed. Results:1 The expression level of Ang-1, Ang-2, Tie-2 mRNA in leukemia1.1 Ang-1, Ang-2, Tie-2 mRNA expression in AML is higher than that in NC and in AML-CR patients (P<0.05). The positive <WP=9>percentage of Ang-1, Ang-2, Tie-2 mRNA expression in AML patients is 64% (32/50), 42% (21/50) and 36% (18/50), respectively. The expression level (ratio of Ang-1, Ang-2, Tie-2 mRNA expression to β-actin mRNA) of these genes is 0.533, 0.280 and 0.266 respectively.1.2 Ang-2, Tie-2 mRNA expression in ALL are the same as in AML (P>0.05), but Ang-1 expression is lower than that in AML (P<0.05). Ang-1, Ang-2, Tie-2 mRNA expression positive percentage and level are 30%, 40%, 40% and 0.070, 0.353, 0.248 respectively.1.3 Ang-1, Ang-2, Tie-2 mRNA expression level in CML-CP is the same as in AML, but lower than that in CML-BP (but no statistics significance because of the small number of samples). The expression positive percentage and level are 66.7%, 33.3%, 33.3%, and 0.425, 0.220,0.193,respectively.1.4 Ang-1, Ang-2 and Tie-2 mRNA expression in relapsed patients with AML is higher than in NC (P<0.05) and is the same as in de novo patients (P>.05). The expression level is 0.497, 0.247, 0.216, for these genes, respectively.1.5 In the myeloid cell lines, Ang-1 is expressed in NB4、K562 and KGa-1; Ang-2 is expressed in KG-1a; but none of them in the HL-60.2 The CR rate of AML in Ang-1 positive patients (62.5%) is lower than that in the negative group (88.9%), P<0.05. The CR rate of AML in Ang-2 positive patients (61.9%) is lower than that in the negative group (79.3%),

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CLC: > Medicine, health > Oncology > Hematopoietic and lymphoid neoplasms > Leukemia
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