Model of telomere biology in CML.

Note that telomeres are shorter in Ph⁺ cells as compared to Ph⁻ normal cells at diagnosis compatible with a greater number of accumulated cell divisions in the Ph⁺stem cell clone. During CP, and with continued proliferation of the Ph⁺ stem cells, the differences in telomere length between Ph⁺ and Ph⁻ cells are expected to become more pronounced. Eventually, the telomeres in the cells of the neoplastic clone become critically short. The resulting chromosomal instability may facilitate progression of the disease to AP/BP. Up-regulation of telomerase at this stage could eliminate telomere-related restrictions in cellular proliferation and is expected to prevent further telomere-mediated genetic instability.