PRELEUKEMIA IN LONG-TERM PLASMACYTOMA-REGRESSOR MICE

Our previous results have indicated that mice whose plasmacytoma regre ssed following curative melphalan chemotherapy manifested various pers istent immunohematological abnormalities including immunosuppression, myeloproliferation, as well as excessive production of and response to growth factors. Mice not bearing plasmacytoma treated with an identic al dose of melphalan chemotherapy did not exhibit such abnormalities. In the present study we show that plasmacytoma-regressor mice (PRM) co ntain preleukemic cells which do not progress to leukemia in these mic e. However, adoptive transfer of splenocytes originating in PRM to pre irradiated but otherwise untreated syngeneic recipients resulted in th e development of overt leukemia in these recipients. The presence of l eukemia in the primary recipient mice was ascertained by blood counts as well as by spleen histology. Furthermore, splenocytes from the irra diated primary recipients adoptively transferred to non-irradiated sec ondary recipients caused leukemia formation in 100% of the secondary r ecipients. Sex chromosome analysis of the leukemic cells in the irradi ated primary recipients clearly showed that they originated in the PRM donors. Two leukemic lines were established from leukemias developing in the secondary recipients and both expressed surface markers of hem atopoietic progenitor cells as well as markers of T cells. We suggest that PRM could serve as an animal model to investigate development of chemotherapy-related leukemia in humans. (C) 1998 Wiley-Liss, Inc.