| Objective: VEGF, the most important factor in angiogenesis which is implicated in neoplasms growth, invasion and metastasis, can induce endothelial cells to proliferate and migrate, and enhance endothelial cells' functions. Abnormal expression of VEGF has been reported in several acute leukemia (AL) cell lines and may participate in leukaemogenesis via an autocrine and/or paracrine fashion, but little is known in clinical AL patients. By our studying, we try to explore the function and clinical significance of VEGF in adult AL.Methods: The gene expressions of VEGF, VEGFR-1, VEGFR-2, MCL1 and MRP were measured by RT-PCR and the protein levels of pi 70, bcl-2 and CD34 were examined by FCM analysis in 64 bone marrow samples of adult AL and 18 cases of normal control (NC). In the meantime, the serum VEGF concentrations were measured by quantitative ELISA in 50 adult de novo AL, 11 complete remission (CR) period patients, 9 relapse patients and 18 NC.Results: 1. The expression of VEGF in AL: ?VEGF gene expression in AL patients (mean 1.05, positive rate45.31%) is higher than that of NC (0.22, 16.67%) (P=0.038, P<0.05). The same exists between AML (1.18, 48.98%) and NC (P=0.025, P<0.025), but there is no statistics difference between ALL (0.63, 33.33%) and NC (P=0.606, P=0.419). (2) The serum VEGF concentration in de novo AL patients (mean 255.50 pg/ml) is higher than that of NC 43.89 pg/ml (P=0.000) and there is no difference between CR patients (61.55 pg/ml) and NC (P=0.323). The level in relapse patients (626.67 pg/ml) is higher than that of both NC and newly diagnosed AL (P=0.000, P=0.000). (3) There is a positive correlation between VEGF gene expression and protein level (r=0.675, P=0.000).2. The expression of VEGFR-1 in AL (positive rate 35.94%) is higher than that of NC 11.11% (P<0.05), but no difference of expression of VEGFR-2 between AL (14.06%) andNC(P>0.05).3. The resistant patients have higher VEGF levels than sensitive patients (P=0.000). The remission rate is lower and the relapse rate is higher in patients with high VEGF levels than the others (PO.025, P=0.005). The VEGF levels may have influence on the relapse rates and overall survival periods (P=0.004, P=0.000).4. The expression of antiapoptosis gene MCL1 in AL (mean 0.94, positive rate 40.63%) is higher than that of NC 0.11, 11.11% (P=0.038, P<0.05). A positive correlation was observed between VEGF expression and MCL1 expression(r=0.552, P=0.000), but no statistics significance between VEGF and bcl-2, p 170 or MRP (P=0.159, P=0.138, P=0.245). 64 AL patients was divided into three parts according to the expressions of VEGF and pi70. The remission rates were significantly different in the three parts (P<0.005)0Conclusion: VEGF and VEGFR-1, with abnormal expression in adult AL, are independent prognosis indexes that play an important role in adult AL. Analysis with MCLl, pi70 and MRP will be more significant to judge response and prognosis in AL. |
PDF Full Text Request