Model for IM-mediated shaping of the BCR-ABL expression repertoire in persisting precursor cells. Immature and mature progenitors express variable levels of BCR-ABL at primary diagnosis of CML (left). BA^high clones are more sensitive to IM, leading to their preferential depletion from bone marrow compartments in optimal responders (A). A delayed depletion of genetically less stable BA^high precursors (B) increases the risk for emergence of secondary mutations and IM resistance (C). Depletion of BA^high and persistence of primarily BA^low progenies would conceivably be required for stable long-term remissions under IM.