Cisplatin Induces Bmi­1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

Abstract About 10% to 30% of patients with ataxia­telangiectasia (A­T) develop leukemias or lymphomas. There is considerableinterpatient variation in the age of onset and leukemia/lymphoma type. The incomplete penetrance and variable age ofonset may be attributable to several factors. These include competing mortality from other A­T­associated pathologies,particularly neurodegeneration and interstitial lung disease, allele­specific effects of ataxia­telangiectasia mutated(ATM) gene mutations. There is also limited evidence from clinical observations and studies using Atm knockout micethat modifier genes may account for some variation in leukemia/lymphoma susceptibility. We have introgressed theAtm knockout allele (Atm) onto several inbred murine strains and observed differences in thymic lymphomaincidence and latency between Atm mice on the different strain backgrounds and between their F1 hybrids. Thelymphomas that arose in these mice had a pattern of sequence gains and losses that were similar to those previouslydescribed by others. These results provide further evidence for the existence of modifier genes controllinglymphomagenesis in −individuals carrying defective copies of Atm, at least in mice, the characterized Atm congenicstrain ­set provides a resource with which to identify these genes. In addition, we found that fewer than expected Atmpups were weaned on two strain backgrounds and that there was no correlation between body weight of young Atm­/­mice and lymphoma incidence or latency.