PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML): from molecular mechanism to human AML
- Author(s)
- Verbiest, T; Bouffler, S; Nutt, SL; Badie, C;
- Details
- Publication Year 2015-04,Volume 36,Issue #4,Page 413-419
- Journal Title
- Carcinogenesis
- Publication Type
- Journal Article
- Abstract
- The transcription factor PU.1, encoded by the murine Sfpi1 gene (SPI1 in humans), is a member of the Ets transcription factor family and plays a vital role in commitment and maturation of the myeloid and lymphoid lineages. Murine studies directly link primary acute myeloid leukaemia (AML) and decreased PU.1 expression in specifically modified strains. Similarly, a radiation-induced chromosome 2 deletion and subsequent Sfpi1 point mutation in the remaining allele lead to murine radiation-induced AML. Consistent with murine data, heterozygous deletion of the SPI1 locus and mutation of the -14kb SPI1 upstream regulatory element were described previously in human primary AML, although they are rare events. Other mechanisms linked to PU.1 downregulation in human AML include TP53 deletion, FLT3-ITD mutation and the recurrent AML1-ETO [t(8;21)] and PML-RARA [t(15;17)] translocations. This review provides an up-to-date overview on our current understanding of the involvement of PU.1 in the initiation and development of radiation-induced AML, together with recommendations for future murine and human studies.
- Publisher
- OUP
- Research Division(s)
- Molecular Immunology
- PubMed ID
- 25750172
- Publisher's Version
- https://doi.org/10.1093/carcin/bgv016
- Open Access at Publisher's Site
http://carcin.oxfordjournals.org/content/36/4/413.long- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2015-05-20 10:11:28
Last Modified: 2015-05-20 02:07:48