LEUKEMIC TRANSFORMATION OF IMMORTALIZED FDC-P1 CELLS ENGRAFTED IN GM-CSF TRANSGENIC MICE

Injection of 10(6) immortalized, but non-leukemic, granulocyte-macroph age colony-stimulating factor (GM-CSF)-dependent FDC-P1 cells into GM- CSF transgenic hybrid mice with elevated GM-CSF levels led to death wi thin three months with elevated blast cell numbers in the blood, massi ve organ infiltration by blast cells, and associated anemia and thromb ocytopenia. No disease developed within this period in littermate mice injected with 10(6) FDC-P1 cells. All moribund transgenic recipients contained transformed FDC-P1 cells able to produce rapidly-growing tra nsplanted leukemias in syngeneic normal DBA/2 recipients. The leukemia s appeared to arise in the primary recipients by independent transform ation events. The transformed cells from different mice differed in th eir in vitro growth characteristics, their ability to produce GM-CSF o r multipotential CSF, and in the nature of the transplanted tumors der ived from the primary cells. While all primary recipients at death con tained fully transformed leukemic cells, the bulk of the large populat ion of FDC-P1 cells appeared either to be untransformed or to have alt ered characteristics not yet representing full transformation. If the FDC-P1 engrafted model has some validity for myelodysplasia, the resul ts suggest that sustained CSF administration to myelodysplastic patien ts possessing abnormal, potentially preleukemic, granulocyte-macrophag e populations may increase the risk of death either from accumulated p retransformed or from fully transformed leukemic cells.