TRANSCOBALAMIN-II AND IN-VITRO PROLIFERATION OF LEUKEMIC-CELLS

We have recently shown that antibodies to transcobalamin II (TCII) inh ibit the in vitro growth of human and murine leukemic cells. This anti proliferative strategy targets the uptake of cobalamin (cbl), an essen tial cofactor for two biochemical reactions in humans. To date there h as been no appropriate cell culture model available to study antagonis m of cbl as a potential antiproliferative strategy. We have establishe d cell culture conditions which allow reproducible measurements of cel l proliferation that is dependent on cbl and its carrier protein, TCII . This bioassay has allowed us to demonstrate that several monoclonal antibodies, raised against TCII, are potent inhibitors of cell prolife ration and that excess cbl abrogates this inhibitory effect. Thus, sup porting our hypothesis that interference with cbl uptake or metabolism will result in inhibition of cell proliferation. Furthermore, cbl met abolism appears to provide a useful target for antiproliferative strat egies which now involve the use of inactive cbl analogs. In this revie w, we update our work on the role of targeting TCII and cbl as an anti proliferative strategy for leukemic cells. We suggest that this strate gy may provide a novel direction for anti cancer reagents.