Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.

Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.
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DOI:
10.1182/blood.v96.10.3374.h8003374_3374_3380
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发表时间:
2000-11
期刊:
影响因子:
20.3
通讯作者:
Ruben A. Mesa;C. Hanson;S. V. Rajkumar;G. Schroeder;A. Tefferi
Ruben A. Mesa;C. Hanson;S. V. Rajkumar;G. Schroeder;A. Tefferi
中科院分区:
医学1区
文献类型:
--
作者:
Ruben A. Mesa;C. Hanson;S. V. Rajkumar;G. Schroeder;A. Tefferi

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最近的观察强调了肿瘤内血管生成的生物学相关性及其对预后的潜在影响。骨髓血管生成增加已在多种血液学疾病中得到证实,包括多发性骨髓瘤。研究114例骨髓纤维化伴髓样化生(MMM)患者骨髓血管生成的程度及预后意义。另外还研究了44例无骨髓疾病患者、15例真性红细胞增多症患者和17例原发性血小板增多症患者作为对照组。骨髓微血管密度评估采用半定量方法、视觉微血管分级、视觉计数和计算机图像分析两种单独的定量方法。三种方法对血管生成的估计具有高度可比性。在视觉微血管分级中,70%的MMM患者、33%的真性红细胞增多症患者、12%的原发性血小板增多症患者和0%的正常对照中,骨髓血管生成出现3级或4级的增加。在一项多变量分析中,MMM血管生成增加与脾脏大小增加显著相关,并被发现是总生存的一个重要且独立的危险因素。骨髓血管生成的增加与高细胞和巨核细胞聚集有关。相反,这两个特征与网状蛋白纤维化成反比,而骨髓血管生成的增加与网状蛋白纤维化无关。这些初步研究结果表明,新血管生成是MMM骨髓基质反应的一个组成部分,可能为抗血管生成药物的治疗研究提供有用的预后信息和理论基础。
Recent observations have underscored the biologic relevance of intratumoral angiogenesis and its potential impact on prognosis. Increased bone marrow angiogenesis has been demonstrated in a variety of hematologic disorders, including multiple myeloma. The extent and prognostic significance of bone marrow angiogenesis in 114 patients with myelofibrosis with myeloid metaplasia (MMM) was investigated. A control group of 44 patients without bone marrow disease, 15 patients with polycythemia vera, and 17 patients with essential thrombocythemia was also studied. Bone marrow microvessel density was assessed by a semiquantitative method, visual microvessel grading, and 2 separate quantitative methods, visual count and computerized image analysis. Angiogenesis estimation by all 3 methods was highly comparable. On visual microvessel grading, a grade 3 or 4 increase in bone marrow angiogenesis was demonstrated in 70% of patients with MMM, 33% of patients with polycythemia vera, 12% of patients with essential thrombocythemia, and 0% of normal controls. In a multivariate analysis, increased angiogenesis in MMM correlated significantly with increased spleen size and was found to be a significant and independent risk factor for overall survival. Increases in marrow angiogenesis correlated with hypercellularity and megakaryocyte clumping. In contrast, these 2 features were inversely proportional to reticulin fibrosis, whereas increases in marrow angiogenesis were independent of reticulin fibrosis. These preliminary findings suggest that neo-angiogenesis is an integral component of the bone marrow stromal reaction in MMM and may provide useful prognostic information and a rationale for the therapeutic investigation of anti-angiogenic agents.