血管内皮生长因子及其受体在急性白血病儿童骨髓和血浆中的表达

Expression of vascular endothelial growth factor and its receptors in bone marrow and plasma of children with acute leukemia

目的 血管内皮生长因子(VEGF)与实体瘤的发生、发展和预后相关,但其与儿童急性白血病的 关系尚不明确。本实验通过检测VEGF及其受体fms样酪氨酸激酶受体(Flt 1)及含激酶插入区受体(KDR)在儿 童急性白血病的表达情况,分析它们与儿童急性白血病的发生与预后的关系,为进一步研究抗白血病治疗新靶点 提供思路。方法 采用RT PCR法检测21例初发和复发、20例缓解后白血病患儿和5例健康儿童骨髓单个核细 胞VEGF、Flt 1、KDRmRNA的表达。使用酶联免疫吸附法检测上述患儿及20例正常儿童外周血VEGF蛋白浓度。 结果 健康儿童骨髓单个核细胞均未检测到VEGF及其受体Flt 1,KDR的表达。90%(19/21)初发/复发白血病 患儿骨髓单个核细胞表达VEGF,86%(18/21)表达Flt 1,30%(6/20)缓解后白血病患儿骨髓单个核细胞表达 VEGF,15%(3/20)表达Flt 1,两组差异有显著性(均P<0.001)。初发/复发组VEGF和Flt 1阳性率与正常组 [0%(0/5);0%(0/5)]比较差异有显著性(均P<0.001),而缓解组与正常组比较差异无显著性。两组白血病患 儿未检测到KDR表达。初发/复发组血浆VEGF浓度为405±270pg/mL,高于缓解组(136±98pg/mL,P<0.01) 和正常组(91±41pg/mL,P<0.01)。缓解组与正常组比较差异无显著性。

Objective The expression of vascular endothelial growth factor (VEGF) is associated with the pathogenesis and prognosis of solid tumors, however its relationship to childhood acute leukemia has not yet been identified. This study determined the expression of VEGF and its receptors in children with acute leukemia in order to study their relationships to the activity of childhood acute leukemia.Methods The mRNA of VEGF, and its receptors Flt-1 and KDR were detected in bone marrow mononuclear cells by the reverse transcription-polymerase chain reaction and the plasma VEGF levels were measured using immunoasssay in 21 children with initial or recurrent untreated acute leukemia and 20 leukemia children in complete remission. The bone marrow samples from 5 healthy volunteer children and plasma samples from 20 healthy children were used as the controls.Results VEGF and its receptors were not expressed in the samples from healthy children. KDR mRNA expression was not detected in either healthy or leukemia children. The VEGF mRNA was expressed in 90% of patients with initial/recurrent acute leukemia, which was higher than in patients in complete remission (30%; P<0.001) and healthy children (P<0.001). The patients with acute leukemia also had a significantly higher Flt-1 mRNA expression level (86%) than patients in complete remission (15%; P<0.001) and healthy children (P<0.001). There was no difference in the expression levels of VEGF and Flt-1 between patients in complete remission and healthy children. The plasma VEGF concentration of initial/recurrent patients (405±270 pg/mL) was much higher than that of patients in complete remission (136± 98 pg/mL; P<0.05) and normal controls (91±41 pg/mL; P< 0.01). There was no difference in the plasma VEGF concentrations between the patients in complete remission and healthy children. Conclusions The expression of VEGF and the receptor (Flt-1) may play an important role in the development of childhood leukemia.