Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells
Nuclear positioning of the BACH2 gene in BCR-ABL positive leukemic cells
复制标题
DOI：
10.1002/gcc.20390
复制
发表时间：
2007-01-01
影响因子：
3.7
通讯作者：
Tashiro, Satoshi
中科院分区：
文献类型：
--
作者：
Ono, Atsushi;Kono, Kazuteru;Tashiro, Satoshi
BACH2 是一种 B 细胞特异性转录抑制因子，也被称为 B 细胞恶性肿瘤中的肿瘤抑制因子。伊马替尼（一种用于治疗慢性粒细胞白血病 (CML) 的分子靶向剂）可在 BCR-ABL 阳性淋巴细胞系（包括 BV173）中诱导 BACH2 的表达。在这里，我们表明 BACH2 基因的活性与基因位点的核定位有关。我们通过比较 BACH2 mRNA 低水平（BV173 和 K562）和高水平（NAMALWA）的细胞，检查了 BACH2 基因与着丝粒异染色质（一种转录抑制性亚核区室）的空间关联。与 NAMALWA 细胞相比，BV173 和 K562 细胞中的 BACH2 基因更靠近着丝粒异染色质。在 BV173 细胞中，伊马替尼治疗后 BACH2-着丝粒距离增加至与 NAMALWA 细胞相似的水平。我们还发现马来酸二乙酯（一种氧化应激源）仅在 BV173 细胞中增强了伊马替尼的抗增殖作用。由于 BACH2 通过氧化应激诱导细胞凋亡，因此这些观察结果表明，通过与着丝粒异染色质相互作用而下调 BACH2 基因将参与 BCR-ABL 阳性淋巴白血病的白血病发生。 2006 威利利斯公司
BACH2 is a B-cell-specific transcription repressor and is also know as a tumor suppressor in B cell malignancy. Expression of BACH2 is induced in BCR-ABL positive lymphoid cell lines including BV173 by imatinib, a molecular targeting agent for the treatment of chronic myeloid leukemia (CML). Here we show that the activity of the BACH2 gene is related to the nuclear positioning of the gene loci. We examined the spatial association of the BACH2 gene with the centromeric heterochromatin, a transcriptionally repressive subnuclear compartment, by comparing cells with low (BV173 and K562) and high (NAMALWA) levels of BACH2 mRNA. The BACH2 gene was located closer to the centromeric heterochromatin in BV173 and K562 cells as compared to NAMALWA cells. In BV173 cells, the BACH2-centromere distance increased after imatinib treatment to levels similar to those in NAMALWA cells. We also found that diethylmaleate, an oxidative stressor, enhanced the antiproliferative effect of imatinib in only BV173 cells. Since BACH2 induces apoptosis by oxidative stress, these observations suggest that down-regulation of the BACH2 gene through the interaction with centromeric heterochromatin would take part in leukomogenesis of BCR-ABL positive lymphoid leukemia. 2006 Wiley-Liss, Inc.