Hematopoietic stem cells, leukemic stem cells and chronic myelogenous leukemia.
Blood-related cancers, or leukemias, have been shown to arise from a rare subset of cells that escape normal regulation and drive the formation and growth of the tumor. The finding that these so-called cancer stem cells, or leukemic stem cells (LSC), can be purified away from the other cells in the tumor allows their precise analysis to identify candidate molecules and regulatory pathways that play a role in progression, maintenance, and spreading of leukemias. The analyses of the other, numerically dominant, cells in the tumor, while also interesting, do not directly interrogate these key properties of malignancies. Mouse models of human myeloproliferative disorder and acute myelogenous leukemia have highlighted the remarkable conservation of disease mechanisms between both species. They can now be used to identify the LSC for each type of human leukemia and understand how they escape normal regulation and become malignant. Given the clinical importance of LSC identification, the insights gained through these approaches will quickly translate into clinical applications and lead to improved treatments for human leukemias.
Passegué
Emmanuelle
E
Department of Pathology, StanfordUniversity School of Medicine, Beckman Center, California 94305, USA. passegue@stanford.edu
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D015973:Gene Expression Regulation, Leukemic; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000473:pathology*; D051379:Mice; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D063150:Polycomb Repressive Complex 1; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology
C489421:Bmi1 protein, mouse; D018398:Homeodomain Proteins; C513262:Hoxb4 protein, mouse; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051153:Wnt Proteins; C097899:homeobox protein HOXA9; D063150:Polycomb Repressive Complex 1