Larochelle Andre, Dunbar Cynthia E
Molecular Hematopoiesis Section, Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Clin Invest. 2008 Apr;118(4):1350-3. doi: 10.1172/JCI35326.
The transcription factor homeobox B4 (HOXB4) is a promising agent capable of providing a growth advantage to genetically modified hematopoietic stem and progenitor cells (HSPCs). In this issue of the JCI, Zhang and colleagues overexpressed HOXB4 in HSPCs from large animals using retroviral vectors (see the related article beginning on page 1502). Two years after transplantation, most animals developed leukemia, a consequence of combined HOXB4 and deregulated protooncogene expression. These results highlight the risks of combining integrating vectors and growth-promoting genes for clinical applications.
转录因子同源框B4（HOXB4）是一种有前景的因子，能够为基因改造的造血干细胞和祖细胞（HSPCs）提供生长优势。在本期《临床研究杂志》中，张及其同事使用逆转录病毒载体在大型动物的HSPCs中过表达HOXB4（见第1502页开始的相关文章）。移植两年后，大多数动物患上了白血病，这是HOXB4与原癌基因表达失调共同作用的结果。这些结果凸显了在临床应用中结合整合载体和促生长基因的风险。
