Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells
Pbx1 is a downstream target of Evi-1 in hematopoietic stem/progenitors and leukemic cells
复制标题
DOI：
10.1038/onc.2009.288
复制
发表时间：
2009-12-10
期刊：
影响因子：
8
通讯作者：
Kurokawa, M.
中科院分区：
文献类型：
--
作者：
Shimabe, M.;Goyama, S.;Kurokawa, M.
亲嗜性病毒整合位点-1（Evi-1）是一种核转录因子，在造血干细胞的增殖和维持中起重要作用。Evi-1的异常表达在髓性白血病中经常被发现，并且与患者的存活率差相关。最近，我们报道了候选人的Evi-1在造血干细胞和白血病细胞中共享的靶基因的基因表达谱分析。在这项研究中，我们确定Pbx 1，造血系统恶性肿瘤的原癌基因，作为Evi-1的靶基因。Evi-1的过表达增加了造血干/祖细胞中Pbx 1的表达。Pbx 1启动子区的分析表明，Evi-1上调Pbx 1转录。此外，通过RNAi介导的敲低降低Pbx 1水平显著抑制Evi-1诱导的转化。与此相反，敲低Pbx 1并不损害E2 A/HLF或AML 1/ETO的骨髓转化，这表明Pbx 1是维持Evi-1介导的骨髓转化所必需的。这些结果表明Pbx 1是Evi-1的靶基因，参与Evi-1介导的白血病发生。Oncogene（2009）28，4364-4374; doi：10.1038/onc.2009.288; 2009年9月21日在线发表
Ecotropic viral integration site-1 (Evi-1) is a nuclear transcription factor, which is essential for the proliferation/maintenance of hematopoietic stem cells (HSCs). Aberrant expression of Evi-1 has been frequently found in myeloid leukemia, and is associated with a poor patient survival. Recently, we reported candidate target genes of Evi-1 shared in HSCs and leukemic cells using gene expression profiling analysis. In this study, we identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a target gene of Evi-1. Overexpression of Evi-1 increased Pbx1 expression in hematopoietic stem/progenitor cells. An analysis of the Pbx1 promoter region revealed that Evi-1 upregulates Pbx1 transcription. Furthermore, reduction of Pbx1 levels through RNAi-mediated knockdown significantly inhibited Evi-1-induced transformation. In contrast, knockdown of Pbx1 did not impair bone marrow transformation by E2A/HLF or AML1/ETO, suggesting that Pbx1 is specifically required for the maintenance of bone marrow transformation mediated by Evi-1. These results indicate that Pbx1 is a target gene of Evi-1 involved in Evi-1-mediated leukemogenesis. Oncogene (2009) 28, 4364-4374; doi: 10.1038/onc.2009.288; published online 21 September 2009