A model for the effect of Bach2 subcellular localization inBCR-ABL–positive (Ph+) and –negative (Ph−) cells. In normal conditions, Bach2 is phosphorylated via the PI-3K/S6K pathway and retained in the cytoplasm (left). Under intensive oxidative stress, the signal for Bach2 phosphorylation and the Crm1-dependent nuclear export is abolished; it migrates to the nucleus and inhibits HO-1 transcription, resulting in induction of apoptosis in Ph-negative cells (middle). In contrast, Bcr-Abl constitutively phosphorylates Bach2 via the PI-3K/S6K pathway, preventing its nuclear translocation in response to oxidative stress, allowing Ph-positive cells to survive even if carrying damaged DNA as a consequence of the mutagenic stimulus (right).