Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice
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1 Experimental Therapeutics and Translational Oncology Program, Instituto de Biología Molecular y Celular del Cáncer, CSIC/ Universidad de Salamanca, SALAMANCA, (SPAIN)
2 Institute of Biomedical Research of Salamanca (IBSAL)
3 Departamento de Anatomía Patológica, Universidad de Salamanca
Received: February 29, 2012; Accepted: March 2, 2012; Published: March 8, 2012;
Keywords: cancer, cancer stem cells (CSC), stem cells, mouse models, Telomerase inhibitors, drug discovery
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.
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