A new circulating form of soluble human tissue factor was identified. This new
form of human tissue factor appears to be the result of alternative splicing and
is therefore referred to as "alt-hTF." Alt-hTF mRNA was detected in a cell line,
HL-60. The cDNA region encoding the entire open reading frame of alt-hTF was cloned.
The sequence encoding the alt-hTF mature peptide was expressed in bacteria. alt-hTF
consists of the first 166 amino acids of membrane bound TF, and a 40 amino acid
C-terminal region unique to alt-hTF. Alt-hTF is likely to be a useful target for
compounds to inhibit clotting and to treat disorders associated with elevated TF.
It may also be useful as a target for antibodies selectively reactive with alt-hTF,
to remove it from the circulation for treatment of clotting or other disorders
associated with elevated or abnormal levels of TF, including thrombotic conditions,
cardiovascular disorders, DVT, DIC, and possibly metastatic cancers.