Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia
Increased angiogenesis in the bone marrow of patients with acute myeloid leukemia
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DOI：
10.1182/blood.v95.8.2637.008k07_2637_2644
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发表时间：
2000-04-15
期刊：
影响因子：
20.3
通讯作者：
Mesters, RM
中科院分区：
文献类型：
--
作者：
Padró, T;Ruiz, S;Mesters, RM
血管生成对于实体瘤的进行性生长和生存力的重要性已得到充分证实。相比之下，只有很少的数据可用于血液肿瘤。为了研究血管生成在急性髓性白血病（AML）中的作用，对62例新诊断的未经治疗的AML成人（第0天）的骨髓活检进行了评价。诱导缓解化疗结束后进行进一步研究（诱导化疗第16天，n = 21;完全缓解，n = 20），在至少3个区域中对微血管进行评分（x500视野，0.126 mm（2））使用血管性血友病因子和血栓调节蛋白的免疫组织化学，在每个骨髓标本的代表性切片中观察最高微血管密度，AML患者（0 = 62）的微血管计数显著高于对照患者（n = 22）：中值（四分位距）24.0（21.0-27.8）/x500场vs 11.2（10.0-12.0）/x500场（P < .001），诱导化疗第16天，微血管密度降低60%（44-66）（P <0.001），而在具有大于或等于5%残余原始细胞的发育不良骨髓中仅减少17%（0-37）（两组之间的差异P <0.001）。完全缓解时的骨髓活检显示微血管密度与对照组相同。总之，有证据表明AML患者骨髓中的微血管密度增加，这支持了血管生成在AML中起重要作用的假设。此外，这些发现表明，抗血管生成治疗可能构成AML治疗的新策略。（Blood，2000;95：2637-2644）（C）2000年，美国血液学会。
The importance of angiogenesis for the progressive growth and viability of solid tumors is well established. In contrast, only few data are available for hematologic neoplasms. To investigate the role of angiogenesis in acute myeloid leukemia (AML), bone marrow biopsies from 62 adults with newly diagnosed, untreated AML (day 0) were evaluated. Further studies were done after the completion of remission induction chemotherapy (day 16 of induction chemotherapy, n = 21; complete remission, n = 20), Microvessels were scored in at least 3 areas (x500 field, 0.126 mm(2)) of the highest microvessel density in representative sections of each bone marrow specimen using immunohistochemistry for von Willebrand factor and thrombomodulin, Microvessel counts were significantly higher in patients with AML (0 = 62) compared with control patients (n = 22): median (interquartile range) 24.0 (21.0-27.8)/x500 field vs 11.2(10.0-12.0)/x500 field, respectively (P < .001), On day 16 of induction chemotherapy, microvessel density was reduced by 60% (44-66) (P < .001) in hypoplastic marrows without residual blasts, in contrast to only 17% (0-37) reduction in hypoplastic marrows with greater than or equal to 5% residual blasts (P < .001 for the difference between both groups). Bone marrow biopsies taken at the time of complete remission displayed a microvessel density in the same range as the controls. In conclusion, there is evidence of increased microvessel density in the bone marrow of patients with AML, which supports the hypothesis of an important role of angiogenesis in AML, Furthermore, these findings suggest that antiangiogenic therapy might constitute a novel strategy for the treatment of AML. (Blood, 2000;95:2637-2644) (C) 2000 by The American Society of Hematology.