Factors influencing the time and site of leukemic transformation of factor-dependent cells after injection into irradiated recipient mice.

After cells of the non-tumorigenic-factor-dependent line FDC-PI are injected into irradiated DBA/2 mice a progressive increase occurs in the number of engrafted FDC-PI cells and eventually leukemic transformation occurs. Step-wise increase in the number of cells injected led to an increasingly rapid accumulation of untransformed FDC-PI cells in the hemopoietic organs and some shortening of the pre-leukemic phase. FDC-PI cells explanted from pre-leukemic mice differed from primary FDC-PI cells in that they were able to undergo leukemic transformation in non-irradiated recipients after short latent periods. Pre-leukemic populations contained FDC-PI variants with an improved ability to proliferate in non-irradiated tissues. Co-injection of normal marrow cells delayed the leukemic transformation of injected FDC-PI cells. The accelerating effect of prior irradiation of the recipient on leukemia development was also abrogated when the injection of FDC-PI cells was delayed by several weeks. No specific site of transformation could be determined in mice with very early leukemias. Proliferation of untransformed FDC-PI cells and the emergence of variants with improved adaptation to in vivo conditions appear to be important and possibly necessary steps in the pathogenesis of the disease. Whether the host contributes actively to the final transformation process remains speculative.