Walter Matthew J, Ries Rhonda E, Armstrong Jon R, Park John S, Mardis Elaine R, Ley Timothy J
Department of Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Blood. 2007 Feb 1;109(3):1237-40. doi: 10.1182/blood-2006-07-037465. Epub 2006 Sep 28.
Expression of a bcr-3 isoform of retinoic acid receptor alpha-promyelocytic leukemia (RARalpha-PML) in mice expressing a bcr-1 isoform of PML-RARalpha is associated with increased penetrance of murine acute promyelocytic leukemia (APL) and the frequent acquisition of an interstitial deletion of one copy of mouse chromosome 2 (del(2)). To determine whether the isoform of RARalpha-PML is important for these effects, we created mice that expressed a bcr-1 isoform of RARalpha-PML. Coexpression with the bcr-1 isoform of PML-RARalpha did not increase the penetrance of APL (7 of 45 animals developed APL with PML-RARalpha alone vs 12 of 44 with both transgenes; P=.19). Furthermore, the frequency of del(2) in APL cells from doubly transgenic mice was not different from that of mice expressing PML-RARalpha alone (3 of 6 vs 6 of 12, respectively-P=1.38-compared with 11 of 11 for mice coexpressing PML-RARalpha and bcr-3 RARalpha-PML). The bcr-1 and bcr-3 isoforms of RARalpha-PML, therefore, have different biological activities that may be relevant for the pathogenesis of murine APL.
在表达PML-RARα的bcr-1亚型的小鼠中，维甲酸受体α-早幼粒细胞白血病（RARα-PML）的bcr-3亚型的表达与小鼠急性早幼粒细胞白血病（APL）的发病率增加以及小鼠2号染色体一个拷贝的间质性缺失（del(2)）的频繁发生有关。为了确定RARα-PML的亚型对这些效应是否重要，我们构建了表达RARα-PML的bcr-1亚型的小鼠。与PML-RARα的bcr-1亚型共表达并未增加APL的发病率（单独表达PML-RARα的45只动物中有7只发生APL，而两个转基因都表达的44只动物中有12只发生APL；P = 0.19）。此外，双转基因小鼠的APL细胞中del(2)的频率与单独表达PML-RARα的小鼠没有差异（分别为6只中的3只与12只中的6只，P = 1.38，而共表达PML-RARα和bcr-3 RARα-PML的小鼠为11只中的11只）。因此，RARα-PML的bcr-1和bcr-3亚型具有不同的生物学活性，这可能与小鼠APL的发病机制有关。
