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Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
The leukemogenicity of Hoxa9 depends on alternative splicing.
Leukemia 28, 1838-1843 (2014)
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 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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Acute Myeloid-leukemia; Hematopoietic-cells; Homeobox Gene; Homeodomain; Protein; Mice; Isoforms; Cancer
ISSN (print) / ISBN
0887-6924
e-ISSN
1476-5551
Zeitschrift
Leukemia
Quellenangaben
Band: 28,
Heft: 9,
Seiten: 1838-1843
Verlag
Nature Publishing Group
Verlagsort
London
Begutachtungsstatus
Peer reviewed