title: Clinical perspectives of concepts on neoplastic stem cells and stem cell-resistance in chronic myeloid leukemia.
abstract: In chronic myeloid leukemia (CML), neoplastic stem cells and/or their subclones exhibit resistance against BCR/ABL tyrosine kinase inhibitors (TKIs). Therefore, residual CML stem cells (subclones) in TKI-treated patients are a logical target of therapy, and their elimination is considered a major aim and clue in the development of curative treatment approaches. A number of different mechanisms may underly resistance of CML stem cells against TKIs and other targeted or/and conventional drugs, including stem cell quiescence, expression of drug-transporters, stem cell plasticity, BCR/ABL mutations, overexpression of BCR/ABL and BCR/ABL-independent signalling- and survival-molecules. In this article, possibilities to overcome stem cell resistance in CML by exploiting knowledge on molecular mechanisms that underly the 'stem cell escape' from drug therapy are discussed.
authors.affiliation: Division of Hematology & Hemostaseology, Department of Internal Medicine I, Medical University of Vienna, Austria. peter.valent@meduniwien.ac.at
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.forename: Michael
authors.initials: M
authors.lastname: Deininger
mesh_terms: D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl