Mechanisms controlling pathogenesis and survival of leukemic stem cells.
Stem cells are an integral component of normal mammalian physiology and have been intensively studied in many systems. Intriguingly, substantial evidence indicates that stem cells also play an important role in the initiation and pathogenesis of at least some cancers. In particular, myeloid leukemias have been extensively characterized with regard to stem and progenitor cell involvement. Thus, as a focal point for both scientific and therapeutic endeavors, leukemic stem cells (LSC) represent a critical area of investigation. LSC appear to retain many characteristics of normal hematopoietic stem cells (HSC) as evidenced by a hierarchical developmental pattern, a mostly quiescent cell cycle profile, and an immunophenotype very similar to HSC. Consequently, defining unique properties of LSC remains a high priority in order to elucidate the molecular mechanisms driving stem cell transformation, and for developing therapeutic strategies that specifically target the LSC population. In this review, we discuss emerging concepts in the field and describe how various molecular and cellular characteristics of leukemia cells might be exploited as a means to preferentially ablate malignant stem cells.
Jordan
Craig T
CT
Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 703, NY 14642, USA. craig_jordan@urmc.rochester.edu
Guzman
Monica L
ML
D000208:Acute Disease; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002455:Cell Division; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015195:Drug Design; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008954:Models, Biological; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000166:cytology*; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D015514:Oncogene Proteins, Fusion