CML progression. Stem cells acquire the Philadelphia chromosome. This begins a process of instability, and increased proliferation yielding multiple clones of progenitors. With unchecked Bcr-Abl activity, instability causes genetic alterations, including point mutations in Abl (and elsewhere), and gross cytogenetic changes. This causes a block in differentiation, increased proliferation of primitive cells, and a block of apoptosis. In this model, progression from chronic to blast phase begins from the outset of disease. The ability of TKI to arrest the progression depends on how long Bcr-Abl activity went on unimpeded.