Unoki Motoko, Okutsu Junichi, Nakamura Yusuke
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
Int J Oncol. 2003 Jun;22(6):1217-23.
To elucidate mechanisms leading to acute myelogenous leukemia (AML), to find sensitive markers and novel targets for drug therapy, and to allow choice of suitable chemotherapy for each affected individual, we previously compared expression of mRNA from mononuclear cells of AML patients with that of normal controls using a cDNA microarray. Data from that study identified many genes that were commonly up- or down-regulated in AML cells. Of these, we report here the identification of a novel gene whose expression was increased in 27 (93%) of the 29 AML cases whose PBMC preparations include >70% leukemia cells. The gene product, localized in nuclei, showed several characteristics of transcription factors: five zinc-finger domains, a leucine zipper, and several nuclear localization signals. Its 92.5% identity in amino-acid sequence to the murine penta zinc finger protein (mPZf; gene symbol Zfp91), led us to term it ZFP91. Anti-sense oligonucleotides inhibited expression of ZFP91, suppressed cell growth, and induced apoptosis. Our results suggest that ZFP91 is likely to play an important role in cell proliferation and/or anti-apoptosis, and may serve as a molecular marker for AML.
为阐明导致急性髓系白血病(AML)的机制,寻找药物治疗的敏感标志物和新靶点,并为每例受影响个体选择合适的化疗方案,我们之前使用cDNA微阵列比较了AML患者单核细胞与正常对照的mRNA表达。该研究的数据鉴定出许多在AML细胞中普遍上调或下调的基因。其中,我们在此报告鉴定出一个新基因,在29例PBMC制剂中白血病细胞>70%的AML病例中,有27例(93%)该基因表达增加。该基因产物定位于细胞核,显示出转录因子的几个特征:五个锌指结构域、一个亮氨酸拉链和几个核定位信号。其氨基酸序列与小鼠五锌指蛋白(mPZf;基因符号Zfp91)有92.5%的同一性,因此我们将其命名为ZFP91。反义寡核苷酸抑制ZFP91的表达,抑制细胞生长并诱导凋亡。我们的结果表明,ZFP91可能在细胞增殖和/或抗凋亡中起重要作用,并可能作为AML的分子标志物。