Expression of a bcr-1 isoform of RARalpha-PML does not affect the penetrance of acute promyelocytic leukemia or the acquisition of an interstitial deletion on mouse chromosome 2.
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.
Walter
Matthew J
MJ
Department of Medicine, Division of Oncology, Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110-1093, USA.
Ries
Rhonda E
RE
Armstrong
Jon R
JR
Park
John S
JS
Mardis
Elaine R
ER
Ley
Timothy J
TJ
D000818:Animals; D002872:Chromosome Deletion; D033481:Chromosomes, Mammalian; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D015473:Leukemia, Promyelocytic, Acute / Q000209:etiology / Q000235:genetics*; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D019683:Penetrance; D020033:Protein Isoforms; D051562:Proto-Oncogene Proteins c-bcr / Q000235:genetics*
D015514:Oncogene Proteins, Fusion; D020033:Protein Isoforms; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C496614:Bcr protein, mouse; D051562:Proto-Oncogene Proteins c-bcr