Zhang Youyi, Pillai Geetha, Gatter Kevin, Blázquez Cristina, Turley Helen, Pezzella Francesco, Watt Suzanne M
Stem Cell Laboratory, National Blood Service, Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford OX3 9BQ, UK.
Hum Pathol. 2005 Jul;36(7):797-805. doi: 10.1016/j.humpath.2005.05.015.
We aimed to study the expression of phosphorylated vascular endothelial growth factor receptor 2 (pVEGFR-2), a membrane-bound tyrosine kinase receptor to vascular endothelial growth factor, in 76 cases of leukemia and nonneoplastic myeloproliferative disease and in 8 reactive bone marrows. The microvessel density (MVD) and the expression of both pVEGFR-2 and its ligand, VEGFA, were evaluated in these cases. We used archival cases and immunohistochemistry with a monoclonal antibody generated by us to the autophosphorylation sites in the cytoplasmic tail of VEGFR-2 and von Willebrand factor antibody to evaluate MVD. Our results demonstrate increased expression of this phosphorylated receptor in the neoplastic cells in acute myeloid and lymphoblastic leukemias. This correlated with increased MVD and VEGFA expression by the neoplastic cells. Interestingly, there was nuclear relocation of this receptor in these diseases. This raises the possibility that pVEGFR-2 may be involved in the transcriptional regulation of these leukemias. Small molecule inhibitors to this receptor may therefore be a useful adjunct in the therapy for these diseases.
我们旨在研究磷酸化血管内皮生长因子受体2（pVEGFR-2）的表达情况，pVEGFR-2是血管内皮生长因子的一种膜结合酪氨酸激酶受体。研究对象包括76例白血病和非肿瘤性骨髓增殖性疾病患者以及8例反应性骨髓。我们对这些病例的微血管密度（MVD）以及pVEGFR-2及其配体VEGFA的表达进行了评估。我们使用存档病例，并采用我们自行制备的针对VEGFR-2胞质尾自磷酸化位点的单克隆抗体以及血管性血友病因子抗体进行免疫组织化学检测，以评估MVD。我们的结果表明，在急性髓系白血病和急性淋巴细胞白血病的肿瘤细胞中，这种磷酸化受体的表达增加。这与肿瘤细胞中MVD和VEGFA表达的增加相关。有趣的是，在这些疾病中该受体出现了核转位。这增加了pVEGFR-2可能参与这些白血病转录调控的可能性。因此，针对该受体的小分子抑制剂可能是这些疾病治疗中的一种有用辅助手段。
