Molecular mapping of chromosome 2 deletions in murine radiation-induced AML localizes a putative tumor suppressor gene to a 1.0 cM region homologous to human chromosome segment 11p11-12

Is PU.1 a dosage-sensitive regulator of haemopoietic lineage commitment and leukaemogenesis?

“…An independent analysis of X-irradiation-induced myeloid leukaemia in mice found that 67% of point mutations also targeted the R235 residue [39]. In addition, this group reported loss of both PU.1 alleles as a rare event in X-irradiation-induced myeloid leukaemia [40].…”

Loss of heterozygosity in spontaneous and x-ray-induced intestinal tumors arising in F1 hybridMin mice: Evidence for sequential loss ofApc+ andDpc4 in tumor development

“…LOH analysis using D4Mit, D11Mit, or D18Mit microsatellites purchased from Research Genetics (Huntsville, IL) was performed as detailed previously (Clark et al, 1996;Silver et al, 1999). All other oligonucleotides used for PCR primers were synthesized by Genosys (Cambridge, U.K.).…”

“…PCR experiments were performed as detailed in Clark et al (1996) and reactions conducted on Hybaid thermal cyclers. PCR products were visualized as detailed in Silver et al (1999) and criteria for scoring LOH are as given in Clark et al (1996). Essentially, LOH was recorded when signal intensity of a particular allele was equal to or less than a reconstructed control equivalent to 20% normal F1 tissue contamination (representative example given in Fig.…”

Evidence for clustered tumour suppressor gene loci on mouse chromosomes 2 and 4 in radiation-induced Acute Myeloid Leukaemia

“…Allelic loss on chromosome 2 is found in 495% of mouse r-AML (Hayata et al 1983, Alexander et al 1995, Silver et al 1999, Cleary et al 1999a, Cook et al 2004). The absence of allelic loss (loss of heterozygosity; LOH) on chromosome 2 in primary r-AML that arose in hybrid mice has been either attributed to the presence of 420% contaminating normal cells in the leukaemic spleen used as a source of r-AML DNA (Cleary et al 1999a, Alexander et al 1995, Silver et al 1999, the activation of endogenous mouse mammary tumour virus (MMTV) in SJL mice (Cook et al 2004), or the mis-diagnosis of a mixed lineage lympho-myeloid leukaemia as an r-AML ).…”

“…The absence of allelic loss (loss of heterozygosity; LOH) on chromosome 2 in primary r-AML that arose in hybrid mice has been either attributed to the presence of 420% contaminating normal cells in the leukaemic spleen used as a source of r-AML DNA (Cleary et al 1999a, Alexander et al 1995, Silver et al 1999, the activation of endogenous mouse mammary tumour virus (MMTV) in SJL mice (Cook et al 2004), or the mis-diagnosis of a mixed lineage lympho-myeloid leukaemia as an r-AML ). The PU1 (also known as SPI-1) transcription factor gene on the remaining chromosome 2 was recently shown to be mutated in exon 5 in 86% of (SJ/L6CBA/H) F1 r-AML (Cook et al 2004).…”