Abstract
We have investigated the functional relevance of c-myb expression for DNA synthesis in patients' T-leukemia cells. [3H]Thymidine incorporation assays of 32 patients' leukemia cells exposed in vitro to c-myb sense or antisense oligodeoxynucleotides served to define two groups of patients: a responder group whose leukemia cells showed 2- to 16-fold lower levels of [3H]thymidine incorporation in c-myb antisense-treated cultures than in c-myb sense-treated cultures (20 patients) and a nonresponder group whose cells showed comparable [3H]thymidine incorporation levels in either c-myb sense- or antisense-treated cultures (12 patients). Down-regulation of c-myb mRNA levels in cells exposed to c-myb antisense oligodeoxynucleotides was comparable in both groups of patients, indicating that differential sensitivity to c-myb antisense oligodeoxynucleotides was not due to differential uptake of these oligodeoxynucleotides. DNA polymerase α mRNA levels were down-regulated in cells from the responders but were unaffected in the nonresponder group. These results suggest that c-myb is required for DNA synthesis in cells of many but not all T-leukemia patients and that leukemia cells in which DNA synthesis is not inhibited despite down-regulation of c-myb expression may have undergone some genetic change(s) that obviate(s) the requirement for myb protein.
Footnotes
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↵1 This work was supported by Grants CA46782, CA31566, CA21765 (CORE), CA 33603, and CH-455 from the National Cancer Institute and the American Cancer Society, respectively, and by the American Lebanese Syrian Associated Charities (ALSAC). D. V. was supported by Training Grant CA094859; M. T. M. is the recipient of a fellowship of the Italian Association for Cancer Research (AIRC). B. C. is a scholar of the Leukemia Society of America.
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↵2 To whom requests for reprints should be addressed.
- Received April 10, 1990.
- Accepted August 20, 1990.
- ©1990 American Association for Cancer Research.
Volume 50, Issue 22
