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The Ontario Cancer Institute and Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada M4X 1K9 [Y. K., N. K., T. W. M.], and Hayashibara Biochemical Laboratories, Inc., 675-1, Fujisaki, Okayama 702, Japan [J. M.]
To evaluate the role of the human T-cell-specific tyrosine kinase lck (YT16), we measured the levels of lck expression in thymocytes, peripheral T-cells, and leukemia T-cell lines which are arrested at different stages of thymic differentiation. The results indicate that higher levels of the lck message can be found in total thymocytes and T-cells arrested at Stage III (thymocytes that have rearranged their
, ß, and
chain T-cell receptor genes). A 20-fold lower level of these transcripts, however, can be found in cells derived from Stage I cells (thymocytes with germline
, ß, and
genes), 4 times less messages in Stage II cells (thymocytes with rearranged
and ß chain genes, but with germline
chain genes), and a 4-fold lower amount of RNA in Stage IV cells (mature lymphocytes). Culture of these cells with a variety of inducing reagents indicated that leukemia cell lines of only Stages I and II can be induced to increase their levels of YT16 expression by the addition of tetradecanoyl phorbol-13-acetate. These results suggest that there may be a developmental regulation of these tyrosine kinase messages during T-cell ontogeny. The high level of these transcripts in more mature T-cell leukemia lines suggests that they may primarily play a role in the proliferative controls of these cells.
1 This work is supported by the Medical Research Council of Canada, the National Cancer Institute of Canada, and the National Sciences and Engineering Research Council of Canada.
Received 7/23/87. Revised 11/11/87. Accepted 11/16/87.
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