THE HUMAN TCF-1 GENE ENCODES A NUCLEAR DNA-BINDING PROTEIN UNIQUELY EXPRESSED IN NORMAL AND NEOPLASTIC T-LINEAGE LYMPHOCYTES

The TCF-1 gene encodes a putative transcription factor with affinity f or a sequence motif occurring in a number of T-cell enhancers. TCF-1 m RNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines. In contrast, expression re portedly occurs in multiple nonlymphoid tissues during murine embryoge nesis. We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein. As expected, the TCF-1 p rotein 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. W estern blotting yielded a set of bands ranging from 25 kD to 55 kD, re sulting from extensive alternative splicing. The TCF-1 protein was det ectable in all samples of a set of 22 T-cell malignancies of various s tages of maturation, but was absent from a large number of other hemat ologic 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 expr ession can serve as a pan-T-lineage marker in the diagnosis of lymphoi d malignancies. (C) 1995 by The American Society of Hematology.