The overall emphasis of this laboratory is the study of murine myeloid leukemias. Our group has found a useful model in mice for studying these types of leukemias which should help us to determine 1) progressive steps of myeloid tumor development in vivo and 2) some of the aberrantly expressed oncogenes that can contribute to the transformation of such cells. It is hoped that these studies will provide information which is relevant to the understanding of leukemogenesis in man since the two in vivo derived murine tumors described below have similar morphological and functional properties to tumors commonly occurring in man. Our previous studies had demonstrated that the inflammatory granuloma caused by the injection of pristane into the peritoneal cavity of mice provides a useful system for rapid induction of myeloid tumors by retroviruses. Two retroviral induced tumors that arose in the peritoneal cavity of primed mice were (a) the McML, mature monocyte-macrophage tumors induced by retroviral constructs containing exons 2 and 3 of c-myc cDNA and (b) the MML, promonocytic tumors induced by Moloney murine leukemia virus (M- MuLV) infection and its integration into the c-myb locus. It is not known precisely what makes the granulomatous tissue essential, but it is likely that the inflammatory response recruits potential target cells for transformation from both within and without the peritoneal cavity and produces an environment that is rich in factors that promote cell growth. We have begun to make progress in our attempts 1) to understand the progressive steps in the development of one of the tumors, 2) to determine what is unique about pristane primed mice that allows these diseases to occur and 3) to find a way of inhibiting induction and/or development of the tumors.
