Essential role for telomerase in chronic myeloid leukemia induced by BCR-ABL in mice

Oncotarget. 2012 Mar;3(3):261-6. doi: 10.18632/oncotarget.461.

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.

MeSH terms

  • Animals
  • Antigens, Ly / genetics
  • Cell Proliferation
  • Cell Survival
  • Cell Transformation, Neoplastic / genetics*
  • Cell Transformation, Neoplastic / pathology
  • Disease Models, Animal
  • Fusion Proteins, bcr-abl / genetics
  • Fusion Proteins, bcr-abl / physiology*
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Membrane Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Neoplastic Stem Cells / physiology
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomerase / physiology*
  • Transfection

Substances

  • Antigens, Ly
  • Ly6a protein, mouse
  • Membrane Proteins
  • Fusion Proteins, bcr-abl
  • Telomerase