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Regulation of expression of MLAA-34 gene through transcriptional factors E2F1 and MZF-1

机译:通过转录因子E2F1和MZF-1调节MLAA-34基因的表达

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摘要

Approximately 20% of adult patients with acute myeloid leukemia fail to achieve remission with initial induction chemotherapy, and around half ultimately experience relapse after achieving complete remission. Relapse continues to be a major hurdle in achieving cure after obtaining remission with induction chemotherapy in patients with acute myeloid leukemia. In last two decades, the immunogenic vaccine, involving peptide, protein, or DNA, has brought new perspectives for tumor immunotherapy. MLAA-34 is a newly identified monocytic leukemia-associated antigen. Downregulation of MLAA-34 expression significantly suppressed the proliferation of U937 cells in vitro and increased the spontaneous apoptosis of leukemia. However, the regulatory mechanisms of MLAA-34 gene are still unknown at present. Analysis of the promoter region of the MLAA-34 gene and reporter gene assays revealed that 600 bp core region was responsible for its regulation. In addition, our study indicated that E2F1 acts as a transcription repressor and MZF-1 acts as a transcription activator of the MLAA-34 gene.
机译:大约20%的成年急性髓性白血病患者无法通过最初的诱导化疗实现缓解,大约一半的患者最终在完全缓解后最终复发。在急性髓性白血病患者中,通过诱导化疗获得缓解后,复发仍然是实现治愈的主要障碍。在过去的二十年中,涉及肽,蛋白质或DNA的免疫原性疫苗为肿瘤免疫治疗带来了新的前景。 MLAA-34是一种新近鉴定的单核细胞白血病相关抗原。 MLAA-34表达的下调显着抑制了U937细胞的体外增殖并增加了白血病的自发凋亡。但是,MLAA-34基因的调控机制目前仍不清楚。对MLAA-34基因启动子区域和报告基因分析的分析表明,600 bp核心区域负责其调控。另外,我们的研究表明E2F1充当MLAA-34基因的转录阻遏物,而MZF-1充当MLAA-34基因的转录激活物。

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