ANTIAPOPTOTIC EFFECT OF ECTOPIC TAL1 SCL EXPRESSION IN A HUMAN LEUKEMIC T-CELL LINE/

Aberrant expression of TALI occurs frequently in human T-cell acute ly mphoblastic leukemia, The effect of TALI expression in the T-cell lymp hoid precursor, however, remains unclear, In the current study, we hav e developed TALI stable transfectants in a human immature T-cell lymph oid cell lime. Whereas no effect on proliferation, cell culture densit y or cell cycle was detected, the transfectants were more resistant th an the parental cell line to apoptosis induced by chemotherapeutic age nts including etoposide, daunorubicin, doxorubicin, cytosine arabinosi de, methotrexate and vincristine and also to apoptosis induced by Fas/ CD95 crosslinking. This effect was independent of the cytostatic effec ts of the drugs. The basic domain-deleted transfectants did Plot demon strate altered sensitivity, suggesting that DNA binding was necessary for resistance to apoptosis, The ability to alter the response to a wi de range of cell death-inducing stimuli suggests that TAL1 acts at a l ate stage of the apoptotic cascade. These data therefore provide direc t evidence of an antiapoptotic effect of ectopic TALI expression in re sponse to cytotoxic agents, thus providing insight into its oncogenic function in T-cell acute lymphoblastic leukemia and a novel experiment al model to further investigate the underlying mechanisms. These data also have potential practical significance for cytotoxic therapy of th is disorder.