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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 volume 16, pages 874–885 (2002)Cite this article

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.

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Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science and Culture; by a Grant-in-Aid for the 2nd Term Comprehensive 10-year Strategy for Cancer Control and a Research Grant on Human Genome and Gene Therapy from the Ministry of Health and Welfare; and by the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Drug ADR Relief, R&D Promotion, and Product Review of Japan. HS was an Awardee of Research Resident Fellowships from the Foundation for Promotion of Cancer Research in Japan. We thank M Mori and C Hatanaka for technical assistance.

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  1. H Shimada and H Ichikawa: HS and HI contributed equally to this work

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  1. Cancer Genomics Division, National Cancer Center Research Institute, Tokyo, Japan

    H Shimada, H Ichikawa & M Ohki

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Shimada, H., Ichikawa, H. & Ohki, M. 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 16, 874–885 (2002). https://doi.org/10.1038/sj.leu.2402465

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