Targeting chronic myeloid leukemia stem cells: can transcriptional program be a druggable target for cancers?

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm resulting from acquisition of constitutively active BCR-ABL protein tyrosine kinase in a hematopoietic stem cell (HSC). Though tyrosine kinase inhibitors (TKIs) have changed a fatal disease into manageable disease, most patients cannot discontinue TKI treatment due to persistence of TKI-resistant leukemia stem cells (LSCs). Much effort has been made to find out factors or pathways specifically operating in LSCs to selectively target LSCs, with some promising results at least in preclinical models. In this article, we briefly review the role of Wnt/β-catenin signaling and its related factors in CML LSCs, especially focusing on Tcf1/Lef1 transcription factors, major effectors of Wnt/β-catenin pathway, of which transcriptional program have recently been shown to be targetable with prostaglandin E1.