We show that LDE225 + nilotinib results in reduced CFC re-plating capacity and LTC-IC potential, reduced engraftment of human CD34+ CML cells in immunodeficient mice and prolonged survival with reduced leukaemogenic potential in the transgenic Scl-tTa-BCR-ABL mouse model that is more representative of CP-CML. Here, BCR is linked to chronic myelogenous leukemia, BCR-ABL1 positive.