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急性淋巴细胞白血病骨髓微环境中的血管生成素

Angiopoietins in the bone marrow microenvironment of acute lymphoblastic leukemia.

作者信息

Karakurt Neslihan, Aksu Tekin, Koksal Yasin, Yarali Nese, Tunc Bahattin, Uckan-Cetinkaya Duygu, Ozguner Meltem

机构信息

a Deparment of Pediatric Hematology/Oncology , Ankara Childrens' Hematology/Oncology Education and Research Hospital , Ankara , Turkey.

b Deparment of Pediatric Hematology/Oncology, Stem Cell Laboratory , Ankara Childrens' Hematology/Oncology Education and Research Hospital , Ankara , Turkey.

出版信息

Hematology. 2016 Jul;21(6):325-31. doi: 10.1080/10245332.2015.1125078. Epub 2016 Mar 1.

Abstract

OBJECTIVE

Angiogenesis have implications in leukemia biology. Angiopoietin 1 (Ang 1) is an angiogenic cytokine which is essential in survival and proliferation of endothelial cells. Angiopoietin 2 (Ang 2) promotes dissociation of pericytes and increases vascular permeability and stromal derived factor 1 alpha (SDF 1α) which is a key player in stem cell traffic in the bone marrow (BM), has stimulating effects on angiogenesis as well. Here, we investigated the role of the leukemic BM microenvironment and specifically, the role of SDF 1α-CXCR4 and Ang 1/Ang 2-Tie 2 axes.

METHODS

Here, Ang 1, Ang 2, and SDF 1α levels were measured in the BM plasma and in supernatants of mesenchymal stem/stromal cells (MSCs) of patients with ALL and compared with those of healthy controls.

RESULTS

The results showed that at diagnosis, BM plasma levels of Ang 1 and SDF 1α were significantly low and Ang 2 was high when compared to control values. Remission induction was associated with an increase in Ang 1/Ang 2 ratio and SDF levels in BM plasma.

DISCUSSION

The results suggest that BM microenvironment and leukemic cell-stroma interaction influences the secretion of Ang 1, 2 and SDF 1α, thus, may affect both angiogenesis, homing and mobilization of leukemic blasts.

摘要

目的

血管生成在白血病生物学中具有重要意义。血管生成素1(Ang 1)是一种血管生成细胞因子,对内皮细胞的存活和增殖至关重要。血管生成素2(Ang 2)促进周细胞解离,增加血管通透性,而基质衍生因子1α(SDF 1α)是骨髓(BM)中干细胞迁移的关键因子,对血管生成也有刺激作用。在此,我们研究了白血病BM微环境的作用,特别是SDF 1α-CXCR4和Ang 1/Ang 2-Tie 2轴的作用。

方法

在此,我们检测了急性淋巴细胞白血病(ALL)患者BM血浆和间充质干/基质细胞(MSCs)上清液中Ang 1、Ang 2和SDF 1α的水平,并与健康对照者进行比较。

结果

结果显示,在诊断时,与对照值相比,BM血浆中Ang 1和SDF 1α水平显著降低,而Ang 2水平升高。缓解诱导与BM血浆中Ang 1/Ang 2比值和SDF水平的升高有关。

讨论

结果表明,BM微环境和白血病细胞-基质相互作用影响Ang 1、2和SDF 1α的分泌,因此,可能影响白血病细胞的血管生成、归巢和动员。

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