Negaard H F S, Iversen N, Bowitz-Lothe I M, Sandset P M, Steinsvik B, Ostenstad B, Iversen P O
Department of Haematology, Ullevål University Hospital Trust, Oslo, Norway.
Leukemia. 2009 Jan;23(1):162-9. doi: 10.1038/leu.2008.255. Epub 2008 Sep 18.
Antiangiogenic drugs are currently tested in haematological malignancies. As these drugs target different angiogenic regulators, and as cancers are inherently heterogeneous, a detailed characterization of angiogenesis in individual cancers is needed. Hence, we measured bone marrow microvessel density (MVD), plasma concentrations of eight angiogenesis-related parameters and the expression in blood mononuclear cells of 40 angiogenesis-related mRNAs in 93 patients with haematological neoplasias (acute myeloid leukaemia; chronic lymphatic leukaemia; multiple myeloma (MM); or non-Hodgkin's lymphoma (NHL)) before start and after completion of cancer therapy. Compared with healthy individuals, the patients had significantly increased bone marrow MVD, especially patients with advanced stage disease. A novel finding was that patients with NHL also had increased bone marrow MVD. The plasma levels of vascular endothelial growth factor (VEGF), interleukin (IL)-6 and IL-8 were significantly increased. VEGF levels were highest in those who did not achieve complete remission after cancer therapy. The mRNA expression of IL-8 was upregulated 15-fold. Our data show that patients with haematological malignancies have increased bone marrow MVD; hence, supporting the notion that bone marrow angiogenesis plays a role in the pathogenesis and progression of these cancers. VEGF, IL-6 and IL-8 seem to contribute to the malignant phenotype.
抗血管生成药物目前正在血液系统恶性肿瘤中进行测试。由于这些药物靶向不同的血管生成调节因子，且癌症本质上具有异质性，因此需要对个体癌症中的血管生成进行详细表征。因此，我们在93例血液系统肿瘤（急性髓系白血病、慢性淋巴细胞白血病、多发性骨髓瘤（MM）或非霍奇金淋巴瘤（NHL））患者开始癌症治疗前和治疗结束后，测量了骨髓微血管密度（MVD）、8种血管生成相关参数的血浆浓度以及40种血管生成相关mRNA在血液单核细胞中的表达。与健康个体相比，患者的骨髓MVD显著增加，尤其是晚期疾病患者。一个新发现是，NHL患者的骨髓MVD也有所增加。血管内皮生长因子（VEGF）、白细胞介素（IL）-6和IL-8的血浆水平显著升高。VEGF水平在癌症治疗后未实现完全缓解的患者中最高。IL-8的mRNA表达上调了15倍。我们的数据表明，血液系统恶性肿瘤患者的骨髓MVD增加；因此，支持了骨髓血管生成在这些癌症的发病机制和进展中起作用的观点。VEGF、IL-6和IL-8似乎促成了恶性表型。
