Release of spleen focus-forming virus (SFFV) from differentiation inducible promyelocytic leukemia cell lines transformed in vitro by friend leukemia virus

Abstract

Three clonally derived sublines of acute promyelocytic leukemia (APML) induced in mouse long-term marrow cultures by Friend leukemia virus (FLV) were examined for release of spleen focus-forming virus (SFFV) and differentiation to mature granulocytes following in vitro exposure to chemical-inducing agents or transfer in vivo to diffusion chambers in irradiated rats or mice. Two APML lines derived from NIH Swiss mouse marrow cultures infected with FLV-anemia-inducing strains (FLV-A) and one line from C3H/HeJ mouse marrow cultures infected with a clonal Rauscher helper virus pseudotype of a cloned SFFV derived from FLV-polycythemia inducing strain (FLV-P) released biologically active SFFV after 18 months growth in suspension culture. In contrast, none of 75 cultures of NIH Swiss or C3H/HeJ bone marrow infected with Rauscher helper virus alone generated permanent APML cell lines or released detectable SFFV from short-term suspension cultures of granulocytic cells. Each line was comprised of 95–99% promyelocytes which required WEHI-3 dialyzed conditioned medium (DCM) for replication in suspension or colony formation in semisolid medium. NIH Swiss APML lines were normal diploid 38XX while the C3H/HeJ line was hypodiploid with 39 chromosomes. Differentiation to mature polymorphonuclear leukocytes was not detected with chemical inducers in vitro but was detected after exposure to irradiated rat plasma or growth in diffusion chambers in vivo. The release of SFFV from FLV-transformed clonal APML cells provides evidence for involvement of this virus in malignant transformation of the granulocyte pathway.