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Blood, 15 May 2004, Vol. 103, No. 10, pp. 3890-3896.
Prepublished online as a Blood First Edition Paper on January 15, 2004; DOI 10.1182/blood-2003-10-3695.
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NEOPLASIA
TEL-AML1 promotes development of specific hematopoietic lineages consistent with preleukemic activity
Michelle Morrow,
Sarah Horton,
Dimitris Kioussis,
Hugh J. M. Brady, and
Owen Williams
From the Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, United Kingdom; and the Division of Molecular Immunology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.
The t(12;21)(p13;q22) translocation is the most common chromosomal abnormality yet identified in any pediatric leukemia and gives rise to the TEL-AML1 fusion product. To investigate the effects of TEL-AML1 on hematopoiesis, fetal liver hematopoietic progenitor cells (HPCs) were transduced with retroviral vectors expressing this fusion protein. We show that TEL-AML1 dramatically alters differentiation of HPCs in vitro, preferentially promoting B-lymphocyte development, enhancing self-renewal of B-cell precursors, and leading to the establishment of long-term growth factor–dependent pre–B-cell lines. However, it had no effect on myeloid development in vitro. Further experiments were performed to determine whether TEL-AML1 also demonstrates lineage-specific activity in vivo. TEL-AML1–expressing HPCs displayed a competitive advantage in reconstituting both B-cell and myeloid lineages in vivo but had no effect on reconstitution of the T-cell lineage. Despite promoting these alterations in hematopoiesis, TEL-AML1 did not induce leukemia in transplanted mice. Our study provides a unique insight into the role of TEL-AML1 in leukemia predisposition and a potential model to study the mechanism of leukemogenesis associated with this fusion.
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