Cell Mol Life Sci：急性髓细胞白血病中VEGF信号

近日，一项最新研究论文阐明了血管内皮生长因子信号（VEGF）在急性髓细胞白血病（AML）中的相关作用。在AML患者骨髓中血管内皮生长因子信号是异常的，其与癌症患者预后较差有关。信号转导通路的改变表现为存在多个自分泌和旁分泌信号通路共同干预。

血管内皮生长因子信号促进急性髓细胞白血病细胞增殖、生存以及抵抗化疗，产生耐药性。
此外在急性髓细胞白血病中，血管内皮生长因子信号可以调解血管内皮细胞的旁分泌控制血管生成。

这两种效应或许可以用来解释高VEGF水平和癌症患者治疗效果不佳的内在联系。最近，重点对骨髓干细胞巢的研究表明血管内皮生长因子信号对几种类型癌症细胞巢的维持是非常必要的。骨髓巢被认为是白血病细胞患者复发的始动因子，为癌症细胞提供了生存的微环境。这意味着在白血病治疗中针对复杂的血管内皮生长因子策略来开展针对性疗法很重要。

该研究针对目前了解的在白血病中异常的血管内皮生长因子信号，揭示了血管内皮生长因子信号干扰肿瘤相关的微环境，并提示目前靶向血管内皮生长因子疗法在临床试验中用于白血病的治疗可能具有新颖性。

编译自：Vascular endothelial growth factor signaling in acute myeloid leukemia

doi:10.1007/s00018-012-1085-3
PMC:
PMID:

Vascular endothelial growth factor signaling in acute myeloid leukemia

Kim R. Kampen, Arja ter Elst and Eveline S. J. M. de Bont

This review is designed to provide an overview of the current literature concerning vascular endothelial growth factor signaling (VEGF) in acute myeloid leukemia (AML). Aberrant VEGF signaling operates in the bone marrow of AML patients and is related to a poor prognosis. The altered signaling pathway demonstrated to interfere in several autocrine and paracrine signaling pathways. VEGF signaling promotes autocrine AML blast cell proliferation, survival, and chemotherapy resistance. In addition, VEGF signaling can mediate paracrine vascular endothelial cell-controlled angiogenesis in AML. Both effects presumably explain the association of high VEGF levels and poor therapeutic outcome. More recently, researches focusing on bone marrow stem cell niches demonstrate a role for VEGF signaling in the preservation of several cell types within these niches. The bone marrow niches are proposed to be a protective microenvironment for AML cells that could be responsible for relapses in AML patients. This implies the need of sophisticated VEGF-targeted therapeutics in AML therapy strategies. This review highlights our current understanding of aberrant VEGF signaling in AML, appoints the interference of VEGF signaling in the AML-associated microenvironment, and reflects the novelty of current VEGF-targeted therapeutics used in clinical trails for the treatment of AML.