EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation.
EVI1 is expressed in megakaryocyte cell lineage and enforced expression of EVI1 in UT-7/GM cells induces megakaryocyte differentiation.
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DOI：
10.1006/bbrc.2002.6693
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发表时间：
2002-04
影响因子：
3.1
通讯作者：
S. Shimizu;T. Nagasawa;O. Katoh;N. Komatsu;J. Yokota;K. Morishita
中科院分区：
文献类型：
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作者：
S. Shimizu;T. Nagasawa;O. Katoh;N. Komatsu;J. Yokota;K. Morishita
3q21q26综合征是一种急性髓系白血病(AML)或骨髓增生异常综合征(MDS)，伴有3q21和3q26之间的染色体易位或倒置，在最初诊断时经常与巨核细胞生成障碍和血小板计数增加有关。由于EVI1基因在3q21q26综合征中被转录激活，我们探讨了EVI1基因表达在3q21q26综合征中巨核细胞分化异常中的作用。对不同类型造血细胞的RT-PCR分析表明，EVI1基因在CD34(+)细胞、巨核细胞和血小板中特异表达。UT-7是一株依赖粒细胞-巨噬细胞集落刺激因子(GM-CSF)(UT-7/GM)生长的人未成熟巨核白血病细胞系，其向红系(UT-7/EPO)和巨核系(UT-7/TPO)的分化能力分别由促红细胞生成素(EPO)和血小板生成素(TPO)诱导。在UT-7/GM、UT-7/EPO和UT-7/TPO三个亚系中，EVI1基因在UT-7/GM和UT-7/EPO细胞中低水平表达，而在UT-7/TPO细胞中表达较高。TPO作用于UT-7/GM细胞后，EVI1表达水平增加，多核巨核细胞数量增加，血小板第4因子(PF-4)基因表达增加。此外，在UT-7/GM细胞中强制表达EVI1基因使其形态改变为多核巨核细胞，停止其生长，并在一个月内诱导细胞死亡。这些数据表明EVI1基因的表达参与了巨核细胞分化的进程，因此，3q21q26综合征的巨核细胞生成障碍可能部分是由于EVI1基因的结构性表达增强了白血病细胞和/或巨核细胞的分化能力。
3q21q26 syndrome, an acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) with chromosomal translocations or inversions between the bands 3q21 and 3q26, is frequently associated with dysmegakaryocytopoiesis and increased platelet counts at the initial diagnosis. Since the EVI1 gene at 3q26 is transcriptionally activated in 3q21q26 syndrome, we assessed the role of EVI1 gene expression in the abnormal megakaryocytic differentiation in 3q21q26 syndrome. RT-PCR analysis of various types of hematopoietic cells revealed that the EVI1 gene is expressed specifically in CD34(+) cells, megakaryocytes, and platelets. UT-7 is a human immature megakaryoblastic leukemia cell line with dependence for the growth on granulocyte-macrophage colony-stimulating factor (GM-CSF) (designated at UT-7/GM) and with a differentiation capacity to erythroid (UT-7/EPO) and megakaryocytic lineages (UT-7/TPO) by erythropoietin (EPO) and thrombopoietin (TPO), respectively. Among three UT-7 sublines, UT-7/GM, UT-7/EPO, and UT-7/TPO, expression of the EVI1 gene was detected at low levels in UT-7/GM and UT-7/EPO cells, but was detected at a higher level in UT-7/TPO cells. When UT-7/GM cells were cultured with TPO, the level of EVI1 expression was increased, along with increased numbers of polynuclear megakaryocytes and expression of the platelet factor 4 (PF-4) gene. Furthermore, forced expression of the EVI1 gene in UT-7/GM cells changed their morphology to polynuclear megakaryocytes, stopped their growth, and induced cell death within a month. These data indicate that expression of the EVI1 gene is involved in progression of megakaryocytic differentiation and, thus, the dysmegakaryocytopoiesis in 3q21q26 syndrome could be partly due to an enhanced differentiation capacity of leukemia cells and/or megakaryocytes by constitutive expression of the EVI1 gene.