Friend leukemia

About: Friend leukemia is a research topic. Over the lifetime, 319 publications have been published within this topic receiving 7463 citations.

The Fli-1 proto-oncogene, involved in erythroleukemia and Ewing's sarcoma, encodes a transcriptional activator with DNA-binding specificities distinct from other Ets family members.

Abstract: The late stages of the erythroleukemias induced by either the replication-defective Friend spleen focus-forming virus (SFFV) or the Friend murine leukemia virus (F-MuLV) are associated with the insertional activation of one of two members (Spi-1 or Fli-1) of the Ets protooncogene family of transcriptional factors. Fli-1 is not rearranged or activated in the erythroleukemias induced by SFFV, and similarly Spi-1 is not rearranged or activated in the leukemic cell clones induced by F-MuLV. This strict specificity of integration sites suggests that Fli-1 and Spi-1 may be functionally distinct and transactivate different downstream genes during the progression of multistage Friend erythroleukemia. In this study, we show that the Fli-1 protein, like other Ets proteins, has DNA-binding activity and can act as a sequence-specific transcriptional activator. We also show that the Fli-1 and Spi-1 proteins are functionally distinct in that they recognize and transactivate through distinct DNA binding sites. Furthermore, we have identified an octanucleotide core sequence that is required in vitro for optimal binding of Fli-1 to the Drosophila E74 target and the promoter sequence of the human GPIIB gene.

Syngeneic adoptive immunotherapy and chemoimmunotherapy of a Friend leukemia: requirement for T cells.

Abstract: The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (104) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-ϑ serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 107 FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-ϑ serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.

Studies on the role of the host immune response in recovery from Friend virus leukemia. II. Cell-mediated immunity.

Abstract: Congenic mouse strains differing only at genes within the H-2 complex were found to have virus-specific cytotoxic effector cells in their spleens during or after recovery from Friend leukemia virus-induced splenomegaly. These effector cells were theta-positive T lymphocytes which functioned in vitro without help or inhibition by B lymphocytes or glass-adherent cells. The antigenic specificities recognized by the effector cells were viral-induced cellular antigens apparently different from those identified by serological techniques.

FBL-reactive CD8+ cytotoxic and CD4+ helper T lymphocytes recognize distinct Friend murine leukemia virus-encoded antigens.

Abstract: Immunization of C57BL/6 (B6) mice with FBL, a Friend murine leukemia virus (F-MuLV), induces both tumor-specific cytolytic CD8+ (CTL) and lymphokine-producing CD4+ Th that are effective in adoptive therapy of B6 mice bearing disseminated FBL leukemia. The current study evaluated the F-MuLV antigenic determinants expressed on FBL that are recognized by FBL-reactive CD8+ and CD4+ T cells. To identify the specificity of the FBL-reactive CD8+ CTL, Fisher rat embryo fibroblast (FRE) cells transfected with plasmids encoding F-MuLV gag or envelope (env) gene products plus the class I-restricting element Db were utilized. FBL-reactive CTL recognized FRE target cells transfected with the F-MuLV gag-encoded gene products, but failed to recognize targets expressing F-MuLV env. Attempts to generate env-specific CD8+ CTL by immunization with a recombinant vaccinia virus containing an inserted F-MuLV env gene were unsuccessful, despite the generation of a cytolytic response to vaccinia epitopes, implying that B6 mice fail to generate CD8+ CTL to env determinants. By contrast, CD4+ Th clones recognized FRE target cells transfected with env and not gag genes, and immunization with the recombinant vaccinia virus induced an env-specific CD4+ T cell response. These data show that in a Friend retrovirus-induced tumor model in which tumor rejection can be mediated by either CTL or Th, antigens derived from discrete retroviral proteins are predominantly responsible for activation of each T cell subset.

Interferon and murine leukemia. I. Inhibitory effect of interferon preparations on development of friend leukemia in mice.

Abstract: SummaryAdministration of concentrated preparations of interferon of high titer (extracted from either mouse brain or serum and spleen) inhibited the development of splenomegaly induced by Friend virus in Swiss and DBA2 mice. Interferon was effective only when treatment was continued daily throughout the duration of the experiment, and when inoculated mtraperitoneally (rather than intravenously).We acknowledge with gratitude the excellent assistance of Mile. Chantal Bourali and Mile. Marie-The rese Thomas. Dr. Raymond Latarjet kindly supplied us with the Friend virus and with a large number of Swiss mice which permitted us to start a colony of these mice. We are indebted to Dr. Charles Chany and to Dr. Rebecca Falcoff for discussion and help in preparation of this report, and to Mr. Philippe Lazar and Mrs. Suzanne Gue guen for analyzing our experimental results and aiding us in their presentation. We should like to thank Dr. John F. Enders for reviewing this manuscript and Dr. Sidney Farber for constant en...