Leukemogenesis in heterozygous PU.1 knockout mice

Genik, Paula C., Vyazunova, I., Steffen, Leta S., Bacher, Jeffrey W., Bielefeldt-Ohmann, Helle, McKercher, Scott, Ullrich, Robert L., Fallgren, Christina M., Weil, Michael M. and Ray, F. Andrew (2014) Leukemogenesis in heterozygous PU.1 knockout mice. Radiation Research, 182 3: 310-315. doi:10.1667/RR13738.1

Author Genik, Paula C.
Vyazunova, I.
Steffen, Leta S.
Bacher, Jeffrey W.
Bielefeldt-Ohmann, Helle
McKercher, Scott
Ullrich, Robert L.
Fallgren, Christina M.
Weil, Michael M.
Ray, F. Andrew
Title Leukemogenesis in heterozygous PU.1 knockout mice
Formatted title
Leukemogenesis in heterozygous PU.1 knockout mice
Journal name Radiation Research   Check publisher's open access policy
ISSN 1938-5404
Publication date 2014-09
Year available 2014
Sub-type Article (original research)
DOI 10.1667/RR13738.1
Open Access Status
Volume 182
Issue 3
Start page 310
End page 315
Total pages 6
Place of publication Lawrence, KS, United States
Publisher Radiation Research Society
Collection year 2015
Language eng
Formatted abstract
Most murine radiation-induced acute myeloid leukemias involve biallelic inactivation of the PU.1 gene, with one allele being lost through a radiation-induced chromosomal deletion and the other allele affected by a recurrent point mutation in codon 235 that is likely to be spontaneous. The short latencies of acute myeloid leukemias occurring in nonirradiated mice engineered with PU.1 conditional knockout or knockdown alleles suggest that once both copies of PU.1 have been lost any other steps involved in leukemogenesis occur rapidly. Yet, spontaneous acute myeloid leukemias have not been reported in mice heterozygous for a PU.1 knockout allele, an observation that conflicts with the understanding that the PU.1 codon 235 mutation is spontaneous. Here we describe experiments that show that the lack of spontaneous leukemia in PU.1 heterozygous knockout mice is not due to insufficient monitoring times or mouse numbers or the genetic background of the knockout mice. The results reveal that spontaneous leukemias that develop in mice of the mixed 129S2/SvPas and C57BL/6 background of knockout mice arise by a pathway that does not involve biallelic PU.1 mutation. In addition, the latency of radiation-induced leukemia in PU.1 heterozygous mice on a genetic background susceptible to radiation-induced leukemia indicates that the codon 235 mutation is not a rate-limiting step in radiation leukemogenesis driven by PU.1 loss.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Veterinary Science Publications
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