title: Alternative approaches to eradicating the malignant clone in chronic myeloid leukemia: tyrosine-kinase inhibitor combinations and beyond.
abstract: In patients with chronic myeloid leukemia (CML) in chronic phase who have achieved complete molecular remission on imatinib therapy, clinical trials from France and Australia have demonstrated that the majority experience prompt molecular relapse of their leukemia upon discontinuation of the drug, showing that long-term monotherapy with tyrosine kinase inhibitors is not curative in the majority of patients with CML. This has focused attention on strategies to eradicate residual disease in CML that is presumed to arise from malignant Ph+ stem cells, which should result in permanent cure and long-term leukemia-free survival. Here, we review the evidence that targeting CML stem cells will be of clinical benefit and discuss pharmacological and immunological approaches to accomplish this goal. Where possible, we link preclinical studies of CML stem cell biology to emerging results from clinical trials of agents that may target these cells.
authors: 1Division of Hematology/Oncology and Molecular Oncology Research Institute, Tufts Medical Center, Boston, MA; and.
authors: Wesam
authors: W
authors: Ahmed
authors: Richard A
authors: RA
authors: Van Etten
mesh_terms: D001315:Australia / Q000453:epidemiology; D001549:Benzamides / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D005602:France / Q000453:epidemiology; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000201:enzymology / Q000473:pathology; D010677:Philadelphia Chromosome; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D015996:Survival Rate
chemical_list: D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate