Inhibition of specific pathways of myeloid cell differentiation by an activated Hox-2.4 homeobox gene.
Abnormal expression of homeobox genes is one of the abnormalities associated with the development of murine and human leukemia. Myeloid leukemic cells that can be induced to differentiate to mature cells by interleukin 6 were stably transfected with an activated Hox-2.4 homeobox gene. Expression of the Hox-2.4 gene in the transfected clones inhibited specific pathways of the myeloid differentiation program induced by interleukin 6. The expression of some genes associated with differentiation was almost completely blocked, and the expression of other genes was either partially inhibited or not affected. The results support the hypothesis that abnormal expression of Hox-2.4 may contribute to the development of leukemia by interfering with the differentiation program.
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
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Blatt
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Lotem
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Sachs
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D005801:Genes, Homeobox; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D018398:Homeodomain Proteins; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology; D007951:Leukemia, Myeloid / Q000473:pathology*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C095822:Hoxb8 protein, mouse; D015850:Interleukin-6; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor