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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / drug effects
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Chromosomes, Human, Pair 21 / genetics
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Chromosomes, Human, Pair 21 / ultrastructure
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Chromosomes, Human, Pair 8 / genetics
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Chromosomes, Human, Pair 8 / ultrastructure
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Core Binding Factor Alpha 2 Subunit
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Gene Expression Regulation, Leukemic*
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Genes, bcl-2
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Granulocyte Colony-Stimulating Factor / pharmacology
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Granulocytes / cytology*
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HL-60 Cells / metabolism
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HL-60 Cells / pathology
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / drug effects
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Hematopoietic Stem Cells / metabolism
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Humans
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Interleukin-3 / pharmacology
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K562 Cells / metabolism
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K562 Cells / pathology
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Leukemia, Myeloid / pathology
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Mice
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Neoplastic Stem Cells / cytology
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Neoplastic Stem Cells / drug effects
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Neoplastic Stem Cells / metabolism
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Oncogene Proteins, Fusion*
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Proto-Oncogene Proteins c-bcl-2 / physiology*
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RUNX1 Translocation Partner 1 Protein
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / physiology
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Recombinant Proteins / pharmacology
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transfection
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Translocation, Genetic
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Tumor Cells, Cultured
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U937 Cells / metabolism
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U937 Cells / pathology
Substances
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AML1-ETO fusion protein, human
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Core Binding Factor Alpha 2 Subunit
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Interleukin-3
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Oncogene Proteins, Fusion
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Proto-Oncogene Proteins c-bcl-2
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RUNX1 Translocation Partner 1 Protein
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Recombinant Fusion Proteins
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Recombinant Proteins
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Transcription Factors
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Granulocyte Colony-Stimulating Factor