The leukemogenicity of Hoxa9 depends on alternative splicing

Tools

Item Type:	Article
Title:	The leukemogenicity of Hoxa9 depends on alternative splicing
Creators Name:	Stadler, C R, Vegi, N, Mulaw, M A, Edmaier, K E, Rawat, V P S, Dolnik, A, Bullinger, L., Heilmeier, B, Quintanilla-Fend, L, Spiekermann, K, Hiddemann, W, Döhner, K, Döhner, H, Feuring-Buske, M and Buske, C
Abstract:	Although the transforming potential of Hox genes is known for a long time, it is not precisely understood to which extent splicing is important for the leukemogenicity of this gene family. To test this for Hoxa9, we compared the leukemogenic potential of the wild-type Hoxa9, which undergoes natural splicing, with a full-length Hoxa9 construct, which was engineered to prevent natural splicing (Hoxa9FLim). Inability to undergo splicing significantly reduced in vivo leukemogenicity compared to Hoxa9-wild-typed. Importantly, Hoxa9FLim could compensate for the reduced oncogenicity by collaborating with the natural splice variant Hoxa9T, as co-expression of Hoxa9T and Hoxa9FLim induced acute myeloid leukemia (AML) after a comparable latency time as wild-type Hoxa9. Hoxa9T on its own induced AML after a similar latency as Hoxa9FLim, despite its inability to bind DNA. These data assign splicing a central task in Hox gene mediated leukemogenesis and suggest an important role of homeodomain-less splice variants in hematological neoplasms.
Keywords:	Acute Myeloid Leukemia, Alternative Splicing, Homeodomain Proteins, Inbred C3H Mice, Inbred C57BL Mice, Animals, Mice
Source:	Leukemia
ISSN:	1476-5551
Publisher:	Nature Publishing Group
Volume:	28
Number:	9
Page Range:	1838-1843
Date:	September 2014
Official Publication:	https://doi.org/10.1038/leu.2014.74
PubMed:	View item in PubMed

Repository Staff Only: item control page