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

M. Britos-Bray, N. Sacchi, A. D. Friedman

Research output: Contribution to journalArticlepeer-review

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 pro teins, consisting of almost exclusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar trunctated 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 CBFβ 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 GCSF. Thus, truncated AML1 proteins may contribute to myeloid leukemogenesis by inhibiting PEBP2/CBF activities, although contributions from other oncoproteins are likely required as well.

Original languageEnglish (US)
Pages (from-to)984-990
Number of pages7
JournalLeukemia
Volume10
Issue number6
StatePublished - Jun 1996

Keywords

  • AML1
  • Differentiation
  • Leukemia
  • Myeloid

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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