Thus LDE225 alone or in combination with nilotinib reduced the primitive leukaemic population as measured by LTC-IC and reduced self-renewal activity as evidenced by re-plating capacity, suggesting that SMO inhibition targets the TKI-insensitive primitive stem/progenitor cell population in CP-CML. Here, SMO is linked to chronic myelogenous leukemia, BCR-ABL1 positive.