Analysis of the expression profile of lineage-specific transcription factors in leukemia cells

加塔-2的表达与造血祖细胞的增殖和分化能力有关，并且抑制加塔-2似乎是造血分化所必需的。因此，阐明加塔-2基因表达调控机制，有助于了解造血细胞分化的早期阶段，并有助于阐明白血病发生的机制。本研究分析了白血病细胞中加塔的表达谱，并分析了加塔-2基因的调控机制。(1)在已建立的白血病细胞系中，加塔-2的表达与CD 34抗原的表达密切相关。为了确定加塔因子的表达谱在造血细胞的恶性对应物中是否被保留或改变，我们分析了来自白血病儿童的原发性白血病原始细胞，并发现肿瘤和相应的正常细胞之间在加塔因子方面的相关性。也就是说，在大多数髓原细胞 ...更多信息 结果：①白血病细胞表达加塔-2 mRNA，表达CD 34和c-kit抗原。相比之下，在淋巴细胞白血病（ALL）患者的CD 34阳性细胞中未检测到加塔-2 mRNA和c-kit抗原。加塔-3 mRNA在所有T-ALL中均表达，而在所有前体B-ALL中均不表达，因此，分析加塔-3基因的表达可能为判断未分型白血病的谱系定型提供有用的工具。(2)我们分离并鉴定了小鼠加塔-2基因，发现加塔-2的表达受两种不同的启动子调控。一种（IG启动子）通常用于表达加塔-2的组织和细胞系中。另一个启动子（IS启动子）特异性地调节加塔-2在造血细胞中的表达。(3)我们使用转基因小鼠检测了小鼠加塔-2基因组位点在体内的调节活性。在IS第一外显子5'端侧翼含有约7 kbp序列的反式基因指导BETA-半乳糖苷酶报告基因特异性地在腹主动脉旁的内脏小胸膜、肝-肝-中肾区和神经组织中表达。原位杂交分析表明，报告基因的表达特异性地再现了加塔-2在这些组织中的内源性表达谱。少

The expression of GATA-2 is related to proliferative versus differentiated capability of hematopoietic progenitor cells, and suppression of GATA-2 seems to be essential for hematopoietic differentiation. Therefore, elucidation of the mechanisms controlling GATA-2 expression may offer insight into the earliest aspects of hematopoietic cellular differentiation and may help clarify the mechanisms underlying leukemogenesis, In the present study, we analyzed GATA expression profiles in leukemia cells and also analyzed the regulatory mechanism of GATA-2 gene.(1) The expression of GATA-2 is closely linked with that of the CD34 antigen in established leukemia cell lines. To ascertain whether the expression profiles of GATA factors are preserved or changed in maligant counterparts of hematopoietic cells, we analyzed primary leukemic blasts from leukemic children, and found a correlation between tumor and respective normal cells in terms of the GATA factors. Namely, in the majority of myelogenou … More s leukemia cases, GATA-2 mRNA expression and the expression of CD34 and c-kit antigens on leukemic cells were demonstrated. In contrast, GATA-2 mRNA and c-kit antigen could not be detected in CD34-positive cells from lymphoblastic leukemia (ALL) patients. GATA-3 mRNA was exressed in all T-ALL cases, but not in any precursor B-ALL.Therefore, exprression analysis of GATA factors may provide a useful tool to determine the lineage commitment of unclassified leukemia.(2) We isolated and characterized the murine GATA-2 gene, and found that GATA-2 expression is regulated by two distinct promoters. One (IG promoter) is used in general in the tissues and cell lines that express GATA-2. The other promoter (IS promoter) regulates the expression of GATA-2 specifically in hematopoietic cells.(3) We examined the regulatory activity of the mouse GATA-2 genomic locus in vivo using transgenic mice. Trans genes containing about 7 kbp of sequence flanking the 5' end of the IS first exon direct expression of BETA-galactosidase reporter gene specifically to the para-aortic splanchnopleula, aorta-ganad-mesonephros region and in the neural tissues, In situ hybridization analysis showed that reporter gene expression specifically recapitulates the endogenaous expression profiles of GATA-2 in these tissues. Less