Stem cell maintenance and disease progression in chronic myeloid leukemia

Chronic myeloid leukemia (CML) is a cancer of blood cells driven by the BCR–ABL1 oncogenic protein tyrosine kinase, which is the product of a reciprocal chromosomal translocation known as the Philadelphia chromosome. Discovery of tyrosine kinase inhibitors targeting the BCR–ABL1 kinase revolutionized CML therapy, but these drugs are unable to eradicate the disease due to the presence of a drug-insensitive stem cell population that sustains continued growth of the malignant cells. Resistance to therapies also increases the risk of relapse and disease progression to a more advanced phase. This review discusses emerging issues in CML research, and describes recent progress in elucidating the mechanisms of CML stem cell maintenance and disease progression.