[Experimental model for differentiation therapy of leukemia]

Recently, a new therapeutic approach to leukemia has been developed by induction of differentiation of leukemic cells. To improve this therapy, various factors involved in in vivo induction of differentiation of leukemia cells should be clarified. Clinical studies showed that inducers of differentiation of leukemia cells including retinoic acid, hexamethylene bisacetamide and some chemotherapeutic drugs induced remission in patients with acute myelogenous leukemia. Clonal analysis of the matured granulocytes revealed that the effectiveness of these drugs was due to their ability to induce differentiation of the leukemic cells rather than their cytocidal activity. On the other hand, various types of agents have been found to induce in vitro differentiation of leukemia line cells and fresh human leukemic cells. To evaluate therapeutic efficacy of these differentiation-inducing agents, pre-clinical experiments using animal model and tests for in vivo inducibility of differentiation of the leukemia cells are essential. We are developing an experimental system to monitor in vivo induction of differentiation of murine leukemia cells inoculated into syngeneic mice.