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The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes

J Castrop, D van Wichen, M Koomans-Bitter, M van de Wetering, R de Weger, J van Dongen and H Clevers

Department of Immunology, University Hospital Utrecht, The Netherlands.

The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers. TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines. In contrast, expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis. We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein. As expected, the TCF-1 protein was detectable only in cell lines of T lineage. Its expression was always restricted to the nucleus. Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues. Western blotting yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive alternative splicing. The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation, but was absent from a large number of other hematologic neoplasms. These observations imply a T cell-specific function for TCF-1, a notion corroborated by recent observations on Tcf- 1 knock-out mice. In addition, these results indicate that nuclear TCF- 1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies.

Volume 86, Issue 8, pp. 3050-3059, 10/15/1995
Copyright © 1995 by The American Society of Hematology


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