BCL6 is required for the initiation and maintenance of chronic myeloid leukemia

We identified the BCL6 protooncogene as a critical downstream effector of FoxO3A in self-renewal signaling of CML-initiating cells. BCL6 represses Arf and p53 in CML cells and is required for leukemia stem cell maintenance, colony formation and initiation of leukemia in transplant recipients. Importantly, peptide inhibition of BCL6 in human CML cells compromises colony formation and leukemia-initiation in xenotransplanted mouse recipients. These findings identify peptide-inhibition of BCL6 as a novel strategy to eradicate leukemia-initiating cells in CML. Identification of BCL6 binding sites in human CML cell line JURL-MK1