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Related Experiment Videos

Model mice for BCR/ABL-positive leukemias.

H Honda1, H Hirai

  • 1Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.

Blood Cells, Molecules & Diseases
|May 19, 2001
PubMed
Summary

Transgenic mice expressing p210 BCR/ABL develop leukemia, mimicking human chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Loss of p53 accelerates disease progression, highlighting its role in CML blast crisis.

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • The p210 BCR/ABL oncoprotein, resulting from the t(9;22) translocation, is a hallmark of chronic myelogenous leukemia (CML) and some acute lymphoblastic leukemia (ALL) cases.
  • Its aberrant kinase activity is central to the pathogenesis of these hematologic malignancies.

Purpose of the Study:

  • To establish an in vivo animal model for BCR/ABL-positive leukemias.
  • To investigate the oncogenic potential of p210 BCR/ABL in a living organism.
  • To explore the role of p53 in the progression of CML from chronic phase to blast crisis.

Main Methods:

  • Generation of transgenic mice expressing p210 BCR/ABL under the control of the mouse tec gene promoter.
  • Crossmating of p210 BCR/ABL transgenic mice with p53 heterozygous mice to generate mice with acquired p53 loss.

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  • Analysis of disease phenotype, latency, and survival in different mouse genotypes.

    • Main Results:

    • Transgenic mice exhibited phenotypes consistent with ALL (founders) or CML-like granulocyte hyperplasia and thrombocytosis (progeny).
    • Mice with combined p210 BCR/ABL expression and acquired p53 loss showed accelerated blast cell proliferation and reduced survival.
    • Preferential loss of the wild-type p53 allele in tumor tissues provided in vivo evidence for p53's role in blastic transformation.

    Conclusions:

    • The generated transgenic mice serve as a valuable model for studying p210 BCR/ABL oncogenicity in vivo.
    • Acquired loss of p53 is a critical factor contributing to the progression of CML to blast crisis.
    • This model offers insights into the molecular mechanisms driving CML pathogenesis and progression.