Block of granulocytic differentiation of 32Dcl3 cells by AML1/ETO(MTG8) but not by highly expressed Bcl-2

Oncogene. 1999 Jul 15;18(28):4055-62. doi: 10.1038/sj.onc.1202735.

Abstract

The chimeric gene, AML1/ETO (MTG8), generated in t(8;21) acute myeloid leukemia enhances the expression of Bcl-2. To evaluate whether this enhancement is the primary role of AML1/ETO in leukemogenesis, effects of over-expression of Bcl-2 in the murine myeloid precursor cell line, 32Dcl3, were examined. When 32Dcl3 cells expressing exogenous Bcl-2 were induced to differentiate, the onset of morphological differentiation was delayed. However, even the cells expressing very high levels of exogenous Bcl-2 eventually underwent differentiation without a significant decrease in the synthesis of Bcl-2. On the contrary, 32Dcl3 cells stably expressing AML1/ETO were completely resistant to differentiation and continued to grow in the presence of G-CSF. These results are consistent with the interpretation that stimulation of Bcl-2 expression is not the primary target of AML1/ETO.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Chromosomes, Human, Pair 21 / genetics
  • Chromosomes, Human, Pair 21 / ultrastructure
  • Chromosomes, Human, Pair 8 / genetics
  • Chromosomes, Human, Pair 8 / ultrastructure
  • Core Binding Factor Alpha 2 Subunit
  • Gene Expression Regulation, Leukemic*
  • Genes, bcl-2
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocytes / cytology*
  • HL-60 Cells / metabolism
  • HL-60 Cells / pathology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Interleukin-3 / pharmacology
  • K562 Cells / metabolism
  • K562 Cells / pathology
  • Leukemia, Myeloid / pathology
  • Mice
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism
  • Oncogene Proteins, Fusion*
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • RUNX1 Translocation Partner 1 Protein
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology
  • Recombinant Proteins / pharmacology
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transfection
  • Translocation, Genetic
  • Tumor Cells, Cultured
  • U937 Cells / metabolism
  • U937 Cells / pathology

Substances

  • AML1-ETO fusion protein, human
  • Core Binding Factor Alpha 2 Subunit
  • Interleukin-3
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins c-bcl-2
  • RUNX1 Translocation Partner 1 Protein
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Transcription Factors
  • Granulocyte Colony-Stimulating Factor