chronic myeloid leukemia as a stem cell-derived malignancy

chronic myeloid leukemia (cml) is a myeloproliferative disease of the hematopoietic stem cells, characterized by the presence of the philadelphia (ph) chromosome. although imatinib inhibits the bcr-abl kinase activity, clinical experiences confirm that imatinib may not target cml stem cells in vivo. the identification of signaling pathways responsible for the self-renewal properties of leukemic stem cells in cml will help in the discovery of novel therapeutic targets. here we review signaling pathways including wnt/β-catenin, hedgehog, alox5, and foxo which play crucial roles in the maintenance of stem cell functions in cml. it is thought that inhibition of key genes that are part of self-renewal associated signaling pathways may provide an effective way to reduce aberrant stem cell renewal in cml.