CML mouse model in translational research

Methods Mol Biol. 2010:602:253-66. doi: 10.1007/978-1-60761-058-8_15.

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without the loss of their capability to differentiate. CML is derived from the hematopoietic stem cells (1) with the Philadelphia chromosome resulting from of a reciprocal translocation between the chromosomes 9 and 22 t(9;22)-(q34;q11). This translocation produces a fusion gene known as BCR-ABL which acquires uncontrolled tyrosine kinase activity, constantly turning on its downstream signaling molecules/pathways, and promoting proliferation of leukemia cell through anti-apoptosis and acquisition of additional mutations. To evaluate the role of each critical downstream signaling molecule of BCR-ABL and test therapeutic drugs in vivo, it is important to use physiological mouse disease models. In this chapter, we describe a mouse model of CML induced by BCR-ABL retrovirus (MSCV-BCR-ABL-GFP; MIG-BCR-ABL) and how to use this model in translational research.

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use
  • Benzamides
  • Bone Marrow Cells / cytology
  • Cell Line
  • Cell Transplantation / methods
  • Disease Models, Animal*
  • Fusion Proteins, bcr-abl* / genetics
  • Fusion Proteins, bcr-abl* / metabolism
  • HSP90 Heat-Shock Proteins / antagonists & inhibitors
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Piperazines / metabolism
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrimidines / metabolism
  • Pyrimidines / therapeutic use
  • Signal Transduction / physiology*
  • Transduction, Genetic
  • Translational Research, Biomedical / methods*

Substances

  • Antineoplastic Agents
  • Benzamides
  • HSP90 Heat-Shock Proteins
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl