| First Author | Jawad M | Year | 2006 |
| Journal | Int J Radiat Biol | Volume | 82 |
| Issue | 6 | Pages | 383-91 |
| PubMed ID | 16846973 | Mgi Jnum | J:122640 |
| Mgi Id | MGI:3714907 | Doi | 10.1080/09553000600784161 |
| Citation | Jawad M, et al. (2006) Evidence for clustered tumour suppressor gene loci on mouse chromosomes 2 and 4 in radiation-induced acute myeloid leukaemia. Int J Radiat Biol 82(6):383-91 |
| abstractText | PURPOSE: To investigate the influence of genetic and epigenetic factors on allelic loss on chromosomes 2 and 4 in mouse radiation-induced acute myeloid leukaemia (r-AML). METHODS: r-AML that arose in (CBA/HxC57BL/6)F1xCBA/H and F1xC57BL/6 mice were screened for transcription factor PU1 (also known as SPI-1) gene mutations and methylation of the paired box gene 5 (Pax5) gene promoter. We have increased the statistical significance of a genetic linkage analysis of affected F1xCBA/H mice to test for linkage to loci implicated directly or indirectly with r-AML-susceptibility. RESULTS: There was a statistically significant difference ( p < 10-4) in the frequency of PU1 gene mutations in F1xCBA/H and F1xC57BL/6 r-AML, implicating a second linked but genotype-dependent myeloid leukaemia suppressor gene on chromosome 2. A suggestive CBA/H r-AML-resistance locus maps within 10 cM of the minimally deleted region on chromosome 4. The Pax5 gene promoter is subject to ongoing subclonal promoter methylation in the r-AML, evidence that Pax5 gene silencing confers a selective advantage during clonal expansion in vivo. CONCLUSIONS: Allelic loss in mouse r-AML and subsequent tumour suppressor gene mutation (PU1) or silencing (Pax5) is strongly influenced by genetic background and/or epigenetic factors, and driven by in vivo clonal selection. |
