Hematopoietic myeloid cell differentiation diminishes nucleotide excision repair
Hematopoietic myeloid cell differentiation diminishes nucleotide excision repair
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DOI：
10.1007/s12185-014-1625-8
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发表时间：
2014-09-01
影响因子：
2.1
通讯作者：
Takagi, Masatoshi
中科院分区：
文献类型：
--
作者：
Aoki, Yuki;Sato, Ayako;Takagi, Masatoshi
髓样细胞分化是干细胞发育成成熟单核细胞或粒细胞的过程。这个过程是通过各种基因的顺序激活来实现的。这一过程的中断可导致免疫缺陷、骨髓衰竭综合征或白血病。急性早幼粒细胞白血病（APL）以t（15;17）易位为特征，可通过全反式维甲酸（ATRA）和蒽环类抗生素的联合治疗。这种治疗可以诱导白血病细胞分化，导致极高的缓解率。XAB 2是一种参与核苷酸切除修复（NER）的分子，在粒细胞分化过程中下调，并在体外NB 4 APL衍生细胞中表达减少。ATRA治疗APL的分化降低体内XAB 2表达水平。这些观察结果表明，细胞分化与降低NER活性，并提供了新的见解组合分化诱导。NB 4细胞比未成熟的髓性白血病细胞系Kasumi-3和Kasumi-1对DNA链间交联剂顺铂更敏感。
Myeloid cell differentiation is the process by which stem cells develop into mature monocytes or granulocytes. This process is achieved by the sequential activation of variety of genes. Disruption of this process can result in immunodeficiency, bone marrow failure syndrome, or leukemia. Acute promyelocytic leukemia (APL) is characterized by the t(15;17) translocation and can be treated by a combination of all-trans retinoic acid (ATRA) and anthracycline. This treatment can induce leukemic cell differentiation, leading to extremely high remission rates. XAB2, a molecule involved in nucleotide excision repair (NER), is downregulated during granulocyte differentiation and shows reduced expression in NB4 APL-derived cells in vitro. Differentiation of APL by ATRA treatment reduced XAB2 expression levels in vivo. These observations suggest that cellular differentiation is associated with reduced NER activity and provides new insights into combined differentiation induction. NB4 cells were more susceptible than the immature myeloid leukemic cell lines, Kasumi-3 and Kasumi-1, to the DNA interstrand crosslinking agent cisplatin.