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Related Experiment Videos

Spi-1/PU.1 transgenic mice develop multistep erythroleukemias

F Moreau-Gachelin1, F Wendling, T Molina

  • 1INSERM U248, Institut Curie, Paris, France.

Molecular and Cellular Biology
|May 1, 1996
PubMed
Summary

Overexpression of the spi-1 gene in mice causes acute erythroleukemia by blocking red blood cell precursor differentiation. This spi-1 (Spi-1) overexpression is essential for malignant erythropoiesis.

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Area of Science:

  • Hematology
  • Oncology
  • Molecular Biology

Background:

  • Insertional mutagenesis of the spi-1 gene is linked to Friend virus-induced acute erythroleukemia.
  • The spi-1/PU.1 transcription factor plays a critical role in hematopoietic development.

Purpose of the Study:

  • To investigate the role of spi-1/PU.1 in leukemia genesis.
  • To determine if spi-1 overexpression is sufficient to induce erythroleukemia.

Main Methods:

  • Generation of spi-1 transgenic mice with transgene overexpression.
  • Analysis of hematopoietic tissues and proerythroblast differentiation in vivo and in vitro.
  • Assessment of disease progression, dependence on erythropoietin, and response to erythrocyte transfusion.

Main Results:

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  • Homozygous transgenic mice developed multistep erythroleukemia, characterized by severe anemia and invasion of nontumorigenic proerythroblasts.
  • Transgenic proerythroblasts showed a partial differentiation block and erythropoietin-dependent proliferation.
  • Disease regression after transfusion suggested spi-1's role in differentiation block; relapse involved erythropoietin-independent malignant proerythroblasts.

Conclusions:

  • Constitutive spi-1 expression is essential for malignant erythropoiesis.
  • While spi-1 overexpression initiates the block in differentiation, additional genetic events are required for full malignant transformation and growth factor autonomy.