DNA-binding domain of AML1, expressed in t(8;21) and t(3;21) myeloid leukemias, inhibits PEBP2/CBF DNA-binding but is not sufficient to transform 32D cl3 myeloid cells

Leukemia. 1996 Jun;10(6):984-90.

Abstract

Truncated AML1 proteins are predicted to be expressed from out-of-frame AML1 transcripts present in myeloid leukemia cells harboring t(8;21) and t(3;21). To test whether these proteins, consisting of almost exclusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar truncated AML1 protein in 32D cl3 myeloid cells. In all clones examined, the ectopically expressed truncated AML1 protein prevented binding of endogenous PEBP2/CBFs to DNA, possibly by interacting with all available CBF beta subunits. However, compared to control clones, the 32D cl3 clones expressing truncated AML1 remained IL-3 dependent for survival, proliferated similarly in low and high concentrations of IL-3, and differentiated similarly upon transfer to G-CSF. Thus, truncated AML1 proteins may contribute to myeloid leukemogeneis by inhibiting PEBP2/CBF activities, although contributions from other oncoproteins are likely required as well.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Blotting, Western
  • Cell Differentiation
  • Cell Transformation, Neoplastic / genetics*
  • Chromosomes, Human, Pair 21*
  • Chromosomes, Human, Pair 3*
  • Chromosomes, Human, Pair 8*
  • Core Binding Factor Alpha 2 Subunit
  • DNA, Neoplasm / metabolism*
  • DNA-Binding Proteins / metabolism*
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Interleukin-3 / pharmacology
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / metabolism
  • Leukemia, Myeloid / pathology
  • Mice
  • Molecular Sequence Data
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Transcription Factor AP-2
  • Transcription Factors / metabolism*
  • Translocation, Genetic*
  • Tumor Cells, Cultured / pathology

Substances

  • Core Binding Factor Alpha 2 Subunit
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • Interleukin-3
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • RUNX1 protein, human
  • Runx1 protein, mouse
  • Transcription Factor AP-2
  • Transcription Factors
  • Granulocyte Colony-Stimulating Factor