title: Molecular mechanisms for survival regulation of chronic myeloid leukemia stem cells.
abstract: Studies on chronic myeloid leukemia (CML) have served as a paradigm for cancer research and therapy. These studies involve the identification of the first cancer-associated chromosomal abnormality and the subsequent development of tyrosine kinase inhibitors (TKIs) that inhibit BCR-ABL kinase activity in CML. It becomes clear that leukemia stem cells (LSCs) in CML which are resistant to TKIs, and eradication of LSCs appears to be extremely difficult. Therefore, one of the major issues in current CML biology is to understand the biology of LSCs and to investigate why LSCs are insensitive to TKI monotherapy for developing curative therapeutic strategies. Studies from our group and others have revealed that CML LSCs form a hierarchy similar to that seen in normal hematopoiesis, in which a rare stem cell population with limitless self-renewal potential gives rise to progenies that lack such potential. LSCs also possess biological features that are different from those of normal hematopoietic stem cells (HSCs) and are critical for their malignant characteristics. In this review, we summarize the latest progress in CML field, and attempt to understand the molecular mechanisms of survival regulation of LSCs.
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Haojian
authors.initials: H
authors.lastname: Zhang
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D051560:Proto-Oncogene Proteins c-bcl-6; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051793:Hypoxia-Inducible Factor 1; D047428:Protein Kinase Inhibitors; D051560:Proto-Oncogene Proteins c-bcl-6; D016044:Fusion Proteins, bcr-abl; D019061:src-Family Kinases