Finally, we provide direct evidence that PIM inhibition results in potent suppression of primitive leukemic progenitors from patients with CML and enhances antileukemic responses to imatinib mesylate in vitro. Notably, pharmacological PIM inhibition appears to exhibit activity against T315I-BCR-ABL1-expressing cells, suggesting that targeting the PIM kinase pathway may provide an approach to overcome resistance to tyrosine kinase inhibitors in CML. Here, PIM1 is linked to chronic myelogenous leukemia, BCR-ABL1 positive.