近日,，一項(xiàng)最新研究論文闡明了血管內(nèi)皮生長(zhǎng)因子信號(hào)（VEGF）在急性髓細(xì)胞白血?。ˋML）中的相關(guān)作用,。在AML患者骨髓中血管內(nèi)皮生長(zhǎng)因子信號(hào)是異常的,，其與癌癥患者預(yù)后較差有關(guān),。信號(hào)轉(zhuǎn)導(dǎo)通路的改變表現(xiàn)為存在多個(gè)自分泌和旁分泌信號(hào)通路共同干預(yù),。
血管內(nèi)皮生長(zhǎng)因子信號(hào)促進(jìn)急性髓細(xì)胞白血病細(xì)胞增殖、生存以及抵抗化療,，產(chǎn)生耐藥性,。
此外在急性髓細(xì)胞白血病中，血管內(nèi)皮生長(zhǎng)因子信號(hào)可以調(diào)解血管內(nèi)皮細(xì)胞的旁分泌控制血管生成,。
這兩種效應(yīng)或許可以用來解釋高VEGF水平和癌癥患者治療效果不佳的內(nèi)在聯(lián)系,。最近，重點(diǎn)對(duì)骨髓干細(xì)胞巢的研究表明血管內(nèi)皮生長(zhǎng)因子信號(hào)對(duì)幾種類型癌癥細(xì)胞巢的維持是非常必要的,。骨髓巢被認(rèn)為是白血病細(xì)胞患者復(fù)發(fā)的始動(dòng)因子,，為癌癥細(xì)胞提供了生存的微環(huán)境。這意味著在白血病治療中針對(duì)復(fù)雜的血管內(nèi)皮生長(zhǎng)因子策略來開展針對(duì)性療法很重要,。
該研究針對(duì)目前了解的在白血病中異常的血管內(nèi)皮生長(zhǎng)因子信號(hào),，揭示了血管內(nèi)皮生長(zhǎng)因子信號(hào)干擾腫瘤相關(guān)的微環(huán)境，并提示目前靶向血管內(nèi)皮生長(zhǎng)因子療法在臨床試驗(yàn)中用于白血病的治療可能具有新穎性,。（生物谷：Bioon.com）
編譯自：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.
