Assembling defenses against therapy-resistant leukemic stem cells: Bcl6 joins the ranks

The resistance of leukemic stem cells in response to targeted therapies such as tyrosine kinase inhibitors (TKIs) relies on the cooperative activity of multiple signaling pathways and molecules, including TGFβ, AKT, and FOXO transcription factors (TFs). B cell lymphoma 6 (BCL6) is a transcriptional repressor whose translocation or mutation is associated with diffuse large BCL. New data now show that BCL6 is critical for the maintenance of leukemias driven by the BCR-ABL translocation (Philadelphia chromosome), suggesting that BCL6 is a novel, targetable member of the complex signaling pathways critical for leukemic stem cell survival.