Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Wash., USA.
Exp Hematol. 2010 Sep;38(9):819-22, 822.e1-3. doi: 10.1016/j.exphem.2010.04.014. Epub 2010 Apr 29.
Retroviral vector proviruses can lead to aberrant expression of nearby genes in hematopoietic repopulating cells, leading to an over-representation of clones with dysregulated genes that affect hematopoiesis. Common integration sites (CISs) identified using the vector provirus as a molecular tag can be used to identify these genes. Here we characterized a retroviral CIS observed at high frequency in baboon hematopoietic repopulating cells that has not been described previously.
Gammaretroviral vector integration sites in baboon repopulating cells identified by polymerase chain reaction amplification were localized to the human genome to identify a CIS. The presence of each clone was tracked over time using allele-specific polymerase chain reaction.
In three different animals that received gammaretrovirally transduced CD34-enriched bone marrow cells, vector proviruses were identified at three distinct sites within a window of 664 base pairs between leupaxin and zinc finger protein 91 (ZFP91). All three integrants of the CIS occurred within a CpG island between leupaxin and zinc finger protein 91 (ZFP91).
We describe a novel CIS between leupaxin and ZFP91 in hematopoietic repopulating cells. Our data suggest that leupaxin and/or ZFP91 may play a role in hematopoietic repopulating cells.
逆转录病毒载体前病毒可导致造血重编程细胞中附近基因的异常表达，导致失调基因影响造血的克隆过度表达。使用载体前病毒作为分子标记识别的常见整合位点（CIS）可用于鉴定这些基因。在这里，我们描述了一种在狨猴造血重编程细胞中高频观察到的、以前未描述过的逆转录病毒 CIS。
通过聚合酶链反应扩增鉴定的狨猴重编程细胞中的γ逆转录病毒载体整合位点被定位到人类基因组中，以鉴定 CIS。使用等位基因特异性聚合酶链反应跟踪每个克隆随时间的存在情况。
在接受γ逆转录病毒转导的 CD34 富集骨髓细胞的三只不同动物中，在 lepaxin 和锌指蛋白 91（ZFP91）之间的 664 个碱基对的窗口内鉴定出三个不同位置的载体前病毒。CIS 的所有三个整合子都发生在 lepaxin 和锌指蛋白 91（ZFP91）之间的 CpG 岛内。
我们描述了造血重编程细胞中 lepaxin 和 ZFP91 之间的一个新的 CIS。我们的数据表明 lepaxin 和/或 ZFP91 可能在造血重编程细胞中发挥作用。
