Vidović Ana, Janković Gradimir, Tomin Dragica, Perunicić-Jovanović Maja, Djunić Irena, Djurasinović Vladislava, Colović Milica
Srp Arh Celok Lek. 2009 Jul-Aug;137(7-8):379-83. doi: 10.2298/sarh0908379v.
Increased angiogenesis in bone marrow is one of the characteristics of chronic myeloid leukaemia (CML), a clonal myeloproliferative disorder that expresses a chimeric bcr/abl protein. Vascular endothelial growth factor (VEGF) is one of the most potent and a specific regulator of angiogenesis which principally targets endothelial cells and regulates several of their functions, including mitogenesis, permeability and migration. The impact of elevated VEGF expression on the course of chronic myeloid leukaemia is unknown.
The aim of this study was the follow-up of VEGF expression during the course of CML.
We studied VEGF expression of 85 CML patients (median age 50 years, range 16-75 years). At the commencement of the study, 29 patients were in chronic phase (CP), 25 in an accelerated phase (AP), and 31 in the blast crisis (BC). The temporal expression (percentage positivity per 1000 analysed cells) VEGF proteins over the course of CML were studied using the immunohistochemical technique utilizing relevant monoclonal antibodies. It was correlated with the laboratory (Hb, WBC and platelet counts, and the percentage of blasts) and clinical parameters (organomegaly, duration of CP, AP, and BC) of disease progression.
The expression ofVEGF protein was most pronounced in AP (ANOVA, p=0.033). The level of VEGF expression correlated inversely with the degree of splenomegaly (Pearson, r=-0.400, p=0.011). High expression of VEGF correlated with a shorter overall survival (log rank, p=0.042).
Immunohistochemically confirmed significance of the expression of VEGF in dependence of the CML stage could be of clinical importance in deciding on the timing therapy. These data suggest that VEGF plays a role in the biology of CML and that VEGF inhibitors should be investigated in CML.
骨髓血管生成增加是慢性髓性白血病（CML）的特征之一，CML是一种表达嵌合型bcr/abl蛋白的克隆性骨髓增殖性疾病。血管内皮生长因子（VEGF）是最有效的血管生成特异性调节因子之一，主要作用于内皮细胞并调节其多种功能，包括有丝分裂、通透性和迁移。VEGF表达升高对慢性髓性白血病病程的影响尚不清楚。
本研究旨在随访慢性髓性白血病病程中VEGF的表达情况。
我们研究了85例慢性髓性白血病患者（中位年龄50岁，范围16 - 75岁）的VEGF表达。研究开始时，29例患者处于慢性期（CP），25例处于加速期（AP），31例处于急变期（BC）。使用免疫组化技术和相关单克隆抗体研究慢性髓性白血病病程中VEGF蛋白的时间表达（每1000个分析细胞中的阳性百分比）。将其与疾病进展的实验室参数（血红蛋白、白细胞和血小板计数以及原始细胞百分比）和临床参数（器官肿大、慢性期、加速期和急变期的持续时间）相关联。
VEGF蛋白表达在加速期最为明显（方差分析，p = 0.033）。VEGF表达水平与脾肿大程度呈负相关（Pearson相关系数，r = -0.400，p = 0.011）。VEGF高表达与总生存期较短相关（对数秩检验，p = 0.042）。
免疫组化证实VEGF表达依赖于慢性髓性白血病分期具有重要意义，这在决定治疗时机方面可能具有临床重要性。这些数据表明VEGF在慢性髓性白血病生物学中起作用，并且应在慢性髓性白血病中研究VEGF抑制剂。
