title: Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice.
abstract: The telomerase protein is constitutively activated in malignant cells from many patients with cancer, including the chronic myeloid leukemia (CML), but whether telomerase is essential for the pathogenesis of this disease is not known. Here, we used telomerase deficient mice to determine the requirement for telomerase in CML induced by BCR-ABL in mouse models of CML. Loss of one telomerase allele or complete deletion of telomerase prevented the development of leukemia induced by BCR-ABL. However, BCR-ABL was expressed and active in telomerase heterozygous and null leukemic hematopoietic stem cells. These results demonstrate that telomerase is essential for oncogene-induced reprogramming of hematopoietic stem cells in CML development and validate telomerase and the genes it regulates as targets for therapy in CML.
authors.affiliation: Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/ Universidad de Salamanca, SALAMANCA, SPAIN.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vicente-Dueñas
authors.forename: Marcos
authors.initials: M
authors.lastname: Barajas-Diego
authors.forename: Isabel
authors.initials: I
authors.lastname: Romero-Camarero
authors.forename: Inés
authors.initials: I
authors.lastname: González-Herrero
authors.forename: Teresa
authors.initials: T
authors.lastname: Flores
authors.forename: Isidro
authors.initials: I
authors.lastname: Sánchez-García
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D019098:Telomerase / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014162:Transfection
chemical_list: D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D016044:Fusion Proteins, bcr-abl; D019098:Telomerase