Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis
Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis
复制标题
急性白血病中 AML1 亚型的过度表达及其在白血病发生中的潜在作用
DOI：
10.1038/leu.2008.350
复制
发表时间：
2009-04-01
期刊：
影响因子：
11.4
通讯作者：
Wang, J.
中科院分区：
文献类型：
--
作者：
Liu, X.;Zhang, Q.;Wang, J.
AML 1/RUNX 1是造血细胞分化和增殖的关键转录因子。从AML 1基因，通过选择性剪接产生至少三种同种型，AML 1a、AML 1b和AML 1c。AML 1a干扰AML 1b/1c的功能，通常称为AML 1。在这项研究中，我们发现与对照组相比，急性淋巴细胞白血病和急性骨髓性白血病（AML）-M2患者中AML 1a的表达水平更高。此外，AML 1a抑制AML 1b介导的巨噬细胞集落刺激因子受体启动子的转录，表明AML 1a拮抗AML 1b的作用。为了研究AML 1a在体内造血和白血病发生中的作用，用AML 1a转导小鼠骨髓单个核细胞，然后将其移植到致死剂量照射的小鼠中，移植后发生淋巴细胞白血病。总之，这些结果表明，AML 1a的过度表达可能是白血病发生的一个重要因素。
AML1/RUNX1 is a critical transcription factor in hematopoietic cell differentiation and proliferation. From the AML1 gene, at least three isoforms, AML1a, AML1b and AML1c, are produced through alternative splicing. AML1a interferes with the function of AML1b/1c, which are often called AML1. In this study, we found a higher expression level of AML1a in acute lymphoblastic leukemia and acute myeloid leukemia (AML)-M2 patients in comparison to the controls. Additionally, AML1a represses transcription of promoter of macrophage colony-stimulating factor receptor mediated by AML1b, indicating that AML1a antagonized the effect of AML1b. To investigate the role of AML1a in hematopoiesis and leukemogenesis in vivo, murine bone marrow mononuclear cells were transduced with AML1a and then transplanted into lethally irradiated mice, which developed lymphoblastic leukemia after transplantation. Taken together, these results indicate that overexpression of AML1a may be an important contributing factor to leukemogenesis.