Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein
Regulation of annexin II by cytokine-initiated signaling pathways and E2A-HLF oncoprotein
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DOI：
10.1182/blood-2003-09-3022
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发表时间：
2004-04-15
期刊：
影响因子：
20.3
通讯作者：
Kurosawa, H
中科院分区：
文献类型：
--
作者：
Matsunaga, T;Inaba, T;Kurosawa, H
在前B细胞急性淋巴细胞白血病（ALL）中，t（17;19）（q22; p13）导致的E2 A-HLF融合基因表达与不良预后、高钙血症和出血并发症相关。我们先前报道E2 A-HLF融合蛋白保护白细胞介素-3（1 L-3）依赖性淋巴细胞免于细胞因子饥饿引起的凋亡。在这里，我们报告膜联蛋白II，一种表面磷脂结合蛋白和急性早幼粒细胞白血病（APL）出血并发症的原因之一，也牵连到t（17;19）（+）ALL。Annexin 11在APL细胞和4个t（17;19）（+）白血病细胞系中均以高水平表达，Annexin II的表达由E2 A-HLF在白血病细胞中的强制表达诱导。在IL-3依赖性细胞中，我们发现膜联蛋白II的表达受IL-3的调节，主要通过Ras途径，包括Ras/磷脂酰肌醇3-激酶途径。此外，E2 A-HLF增加膜联蛋白II在IL-3依赖性细胞中的表达，在细胞因子的情况下。这些发现表明E2 A-HLF通过取代激活Ras下游途径的细胞因子来诱导膜联蛋白II。(C)2004年，美国血液学会。
In pro-B cell acute lymphoblastic leukemia (ALL), expression of the E2A-HLF fusion gene as a result of t(17;19)(q22; p13) is associated with poor prognosis, hypercalcemia, and hemorrhagic complications. We previously reported that the E2A-HLF fusion protein protects interleukin-3 (1L-3)-dependent lymphoid cells from apoptosis caused by cytokine starvation. Here, we report that annexin II, a surface phospholipid-binding protein and one of the proposed causes of the hemorrhagic complications of acute promyelocytic leukemia (APL), is also implicated in t(17;19)(+) ALL. Annexin 11 was expressed at high levels in APL cells and in each of 4 t(17;19)(+) leukemia cell lines, and annexin II expression was induced by enforced expression of E2A-HLF in leukemia cells. In IL-3-dependent cells, we found that annexin II expression was regulated by IL-3 mainly by Ras pathways, including Ras/phosphatidylinositol 3-kinase pathways. Moreover, E2A-HLF increased annexin II expression in IL-3-dependent cells in the absence of the cytokine. These findings indicate that E2A-HLF induces annexin II by substituting for cytokines that activate downstream pathways of Ras. (C) 2004 by The American Society of Hematology.