Potential involvement of the AML1-MTG8 fusion protein in the granulocytic maturation characteristic of the t(8;21) acute myelogenous leukemia revealed by microarray analysis

Leukemia. 2002 May;16(5):874-85. doi: 10.1038/sj.leu.2402465.

Abstract

The AML1 (RUNX1)-MTG8 (ETO) fusion transcription factor generated by the t(8;21) translocation is believed to deregulate the expression of genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors, resulting in acute myelogenous leukemia. To elucidate the role of AML1-MTG8 in leukemogenesis, we used oligonucleotide microarrays to detect alterations in gene expression caused by ectopic expression of AML1-MTG8 in a murine myeloid progenitor cell line, L-G. Microarray analysis of approximately 6500 genes identified 32 candidate genes under the downstream control of AML1-MTG8. Among the 32 genes, 23 were not known to be regulated by AML1-MTG8. These included many granule protein genes and several cell surface antigen genes. Interestingly, AML1-MTG8 enhanced the expression of several genes that are usually induced during granulocytic differentiation, particularly those encoding azurophil granule proteins, including cathepsin G, myeloperoxidase and lysozyme. This indicates that AML1-MTG8 induces partial differentiation of myeloid progenitor cells into promyelocytes in the absence of the usual differentiation signals, while it inhibits terminal differentiation into mature granulocytes. Thus, AML1-MTG8 itself may play a crucial role in defining a unique cytologic type with abnormal maturation, characteristic of t(8;21) acute myelogenous leukemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / drug effects
  • Acute-Phase Proteins / genetics
  • Animals
  • Case-Control Studies
  • Cathepsin G
  • Cathepsins / drug effects
  • Cathepsins / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, Pair 8
  • Core Binding Factor Alpha 2 Subunit
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Granulocytes / drug effects
  • Granulocytes / pathology*
  • Humans
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / pathology*
  • Lipocalin-2
  • Lipocalins
  • Mice
  • Muramidase / drug effects
  • Muramidase / genetics
  • Myeloid Progenitor Cells / cytology
  • Myeloid Progenitor Cells / drug effects
  • Oligonucleotide Array Sequence Analysis*
  • Oncogene Proteins / drug effects
  • Oncogene Proteins / genetics
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / pharmacology
  • Oncogene Proteins, Fusion / physiology*
  • Peroxidase / drug effects
  • Peroxidase / genetics
  • Proto-Oncogene Proteins
  • RUNX1 Translocation Partner 1 Protein
  • Serine Endopeptidases
  • Transcription Factors / genetics
  • Transcription Factors / pharmacology
  • Transcription Factors / physiology*
  • Transduction, Genetic
  • Translocation, Genetic

Substances

  • AML1-ETO fusion protein, human
  • Acute-Phase Proteins
  • Core Binding Factor Alpha 2 Subunit
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Oncogene Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Proteins
  • RUNX1 Translocation Partner 1 Protein
  • Transcription Factors
  • Lcn2 protein, mouse
  • Peroxidase
  • Muramidase
  • Cathepsins
  • Serine Endopeptidases
  • CTSG protein, human
  • Cathepsin G
  • Ctsg protein, mouse