三氧化二砷下调急性髓细胞性白血病患者骨髓细胞中膜联蛋白 II 的表达。

Arsenic trioxide downregulates the expression of annexin II in bone marrow cells from patients with acute myelogenous leukemia.

机构信息

Department of Hematology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430022, China.

出版信息

Chin Med J (Engl). 2009 Sep 5;122(17):1969-73.

PMID:19781379

Abstract

BACKGROUND

Most patients with acute myelogenous leukemia (AML) suffer from disordered hemostasis. We have previously shown that annexin II (Ann II), a high-affinity co-receptor for plasminogen/tissue plasminogen activator, plays a central role in primary hyperfibrinolysis in patients with acute promyelocytic leukemia (APL). The expression of Ann II in cells from patients with major subtypes of AML and the effect of arsenic trioxide (As2O3) on Ann II expression in AML cells were investigated to determine whether As2O3-mediated downregulation of Ann II could restore hemostatic stability.

METHODS

A total of 103 patients (48 females and 55 males; age, 19 - 58 years) were included. Plasma samples were collected before and after treatment as well as after complete remission. Ann II and plasminogen activation were measured in leukemic cells during treatment with 1 micromol/L As2O3.

RESULTS

Before As2O3 treatment, Ann II mRNA expression (real-time PCR) was the highest in M3 cells (P < 0.05), higher in M5 cells than that in M1, M2, M4, and M6 cells (P < 0.001), and positively correlated with Ann II protein expression (flow cytometry) (r = 0.752, P < 0.01). Exposure for up to 120 hours to As2O3 (1 micromol/L) had no significant effect on Ann II protein in M1 and M2 leukemic cells, but decreased Ann II protein expression twofold within 48 hours of exposure in M3 cells (P < 0.05) and twofold within 96 hours in M5 cells (P < 0.05). The rate of plasmin generation was higher in APL, M5, and M4 cells than in M1, M2, and M6 cells.

CONCLUSIONS

As2O3 may reduce hyperfibrinolysis in AML by downregulation of Ann II. Furthermore, As2O3 affects more than one form of AML (APL, M4 and M5), suggesting its potential role in their management.

摘要

背景

大多数急性髓系白血病（AML）患者存在止血功能紊乱。我们之前的研究表明，作为纤溶酶原/组织纤溶酶原激活物的高亲和力辅助受体， annexin II（Ann II）在急性早幼粒细胞白血病（APL）患者的原发性高纤溶中发挥核心作用。本研究旨在检测 Ann II 在 AML 主要亚型细胞中的表达情况，并观察三氧化二砷（As2O3）对 AML 细胞中 Ann II 表达的影响，以确定 As2O3 是否通过下调 Ann II 来恢复止血稳定性。

方法

共纳入 103 例患者（48 名女性和 55 名男性；年龄 19-58 岁）。治疗前后及完全缓解后采集血浆样本。用 1μmol/L 的 As2O3 处理时，检测白血病细胞中 Ann II 和纤溶酶原的激活情况。

结果

在接受 As2O3 治疗前，M3 细胞中的 Ann II mRNA 表达（实时 PCR）最高（P<0.05），高于 M1、M2、M4 和 M6 细胞（P<0.001），且与 Ann II 蛋白表达（流式细胞术）呈正相关（r=0.752，P<0.01）。用 1μmol/L 的 As2O3 处理长达 120 小时对 M1 和 M2 白血病细胞中的 Ann II 蛋白无明显影响，但可使 M3 细胞中的 Ann II 蛋白在 48 小时内降低 2 倍（P<0.05），M5 细胞中的 Ann II 蛋白在 96 小时内降低 2 倍（P<0.05）。APL、M5 和 M4 细胞中的纤溶酶生成率高于 M1、M2 和 M6 细胞。