Cancer Research, 2002 Sept 15;62(18):5153-7
In the September 1st issue of the very prestigious Cancer Research journal appeared a landmark paper written by our research team at M. D. Anderson Cancer Center, Science Park – Research Division. The paper is a landmark because it describes and explains an experiment that has, for the first time, demonstrated that by the proper administration of dexamethasone it is possible to prevent lymphoma in mice with A-T. This finding is of worldwide significance and will open new avenues of investigation.
Needless to say, we are very proud of our researchers for making this discovery and for continuing to pursue its applicability to humans.
Below are excerpts from the paper. If you would like a more detailed scientific explanation of this information or a copy of the paper, requests for reprints should be addressed to the University of Texas M.D. Anderson Cancer Center, Science Park – Research Division, P.O. Box 389, Smithville, TX 78957. Phone: (512) 237-9456; Fax: (512) 237-2444; E-mail: pwong@sprd1.mdacc.tmc.edu.
ABSTRACT:
Prevention of thymic lymphoma development in Atm-/- mice by dexamethasone.
Cancer Research
September 2002
Yan M, Kuang X, Qiang W, Shen J, Claypool K, Lynn WS, Wong PK.
The University of Texas M. D. Anderson Cancer Center, Science Park-Research Division,
Smithville, TX 78957, USA.
We have reported (M. Yan et al., FASEB J., 15: 1132-1138, 2001) that spontaneous DNA synthesisis markedly increased in the thymocytes from the atrophied thymi of young Atm-/- mice. We, therefore, set out to determine whether this elevated DNA synthesis is responsible for the development of thymic lymphomas in all Atm-/- mice by 4-5 months of age. We show here that in Atm-/- mice: (a) increased DNA synthesis occurs, especially in the immature CD4(-) CD8(-) (dominant negative) and CD8(+) thymocyte populations; (b) the relative percentage of dominant negative cells increases significantly during postnatal development, with a sharp peak at 4 weeks of age; and (c) dexamethasone suppresses DNA synthesis in these thymocytes and prevents thymic lymphoma development. These observations suggest that ataxia telangiectasia mutated (ATM) down-regulates the proliferation of thymocytes, allowing T-cell development and differentiation. The results also show that dexamethasone, like ATM, checks DNA synthesis in developing thymocytes. Finally, the data document for the first time that dexamethasone prevents or slows thymic lymphoma development in Atm-/- mice.
PMID: 12234978 [PubMed - indexed for MEDLINE]