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Transcriptional Control And Signal Transduction

The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation

Leukemia volume 21, pages 2010–2019 (2007)Cite this article

Abstract

The 8;21 translocation is a common chromosomal abnormality in acute myeloid leukemia (AML). We recently identified a naturally occurring leukemogenic splice variant, AML1-ETO9a (acute myeloid leukemia-1 transcription factor and the eight-twenty-one corepressor-9a), of t(8;21). To understand the leukemic potential of AML1-ETO9a, we performed microarray analysis with the murine multipotential hematopoietic FDCP-mix A4 cell line. We identified changes in expression of various genes including CD44. CD44 is a type I transmembrane protein and functions as the major cellular adhesion molecule for hyaluronic acid, a component of the extracellular matrix. CD44 is expressed in most human cell types and is implicated in myeloid leukemia pathogenesis. We show that the presence of AML1-ETO9a significantly increased the expression of CD44 at both RNA and protein levels. Furthermore, the CD44 promoter is bound by AML1-ETO9a and AML1-ETO at the chromatin level. In addition, in the AML1-ETO9a leukemia mouse model CD44 is regulated in a cell context-dependent manner. Thus, our observations suggest that AML1-ETO and its splice variant AML1-ETO9a are able to regulate the expression of the CD44 gene, linking the 8;21 translocation to the regulation of a cell adhesion molecule that is involved in the growth and maintenance of the AML blast/stem cells.

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Acknowledgements

We thank Dr Joseph Biggs for critical editing of this manuscript and members of Zhang lab for valuable discussions. The Stein Endowment Fund partially supported the departmental molecular biology service laboratory for DNA sequencing and oligonucleotide synthesis. This is manuscript 18718 from The Scripps Research Institute. This work was supported by National Institute of Health Grant no. CA104509 (DEZ). MCL is a fellow of the Leukemia and Lymphoma Society.

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Author notes

  1. L F Peterson

    Present address: 2Current address: Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.,

  2. L F Peterson and Y Wang: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, USA

    L F Peterson, Y Wang, M-C Lo, M Yan, E Kanbe & D-E Zhang

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Correspondence to D-E Zhang.

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Peterson, L., Wang, Y., Lo, MC. et al. The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation. Leukemia 21, 2010–2019 (2007). https://doi.org/10.1038/sj.leu.2404849

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