PU.1 downregulation in murine radiation-induced acute myeloid leukaemia (AML): from molecular mechanism to human AML

Carcinogenesis
Tom VerbiestC Badie

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.

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Citations

Oct 30, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yong XiePeifu Tang
Sep 8, 2015·Radiation and Environmental Biophysics·Werner RühmNobuyuki Hamada
Nov 10, 2016·International Journal of Molecular Sciences·Tom VerbiestChristophe Badie
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Feb 6, 2017·International Journal of Radiation Biology·R Julian Preston
Feb 10, 2017·Blood·Raman SoodPaul Liu
Jun 2, 2016·Development·Makiko Iwafuchi-Doi, Kenneth S Zaret
Jun 23, 2018·International Journal of Radiation Biology·Melis KarabulutogluChristophe Badie
Jun 3, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei JianYi Qiu
Jan 17, 2019·Oncotarget·Tom VerbiestChristophe Badie
Jan 18, 2019·International Journal of Radiation Biology·Nathalie GaultSimon Bouffler
Nov 13, 2019·Cold Spring Harbor Perspectives in Medicine·Yilin WuHong Wu
Feb 23, 2018·Oncology Letters·Yuanzhi XuMeiqing Lou
Jul 2, 2017·Cellular and Molecular Life Sciences : CMLS·Serge M CandéiasChristophe Badie
Jun 27, 2018·Frontiers in Immunology·Swee Heng Milon PangStephen L Nutt
Nov 23, 2020·Radiation and Environmental Biophysics·Sjors StoutenFieke Dekkers
Mar 14, 2021·Bulletin of Experimental Biology and Medicine·O V KovalevaA N Gratchev

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Methods Mentioned

BETA
gene
X-ray
chromosomal aberration
chromosomal aberrations
deamination
flow cytometry

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