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Friend leukemia

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


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TL;DR: Results show that Spi‐1/PU.1 requires signals emanating from specific cytokine and growth factor receptors to affect the survival, proliferation and differentiation control of primary erythroblasts, and suggest that the function of Spi-1/ PU.1 in the late phase of Friend leukemia requires specific signaling from the gp55‐modified EpoR generated during the early phase of the disease.
Abstract: Spi-1/PU.1 is a myeloid- and B-cell specific transcription factor which is also involved in Friend virus-induced murine erythroleukemia. The pre-leukemic phase of Friend erythroleukemia results from activation of the erythropoietin receptor (EpoR) by the spleen focus forming virus (SFFV) envelope glycoprotein, followed by the emergence of leukemic clones characterized by overexpression of Spi-1 and mutation of the p53 tumor suppressor gene. We developed a heterologous system to analyze the contribution of these alterations to the induction of primary erythroblast transformation. Avian erythroblasts expressing the activated mouse EpoR(R129C) differentiated into erythrocytes in response to hEpo. Expression of Spi-1 in these cells inhibited this ability to differentiate and rescued the cells from the apoptotic cell death program normally induced upon hEpo withdrawal. Although devoid of any effect by itself, a mutant p53 cooperated with Spi-1 and EpoR(R129C) to reinforce both phenotypes. Analysis of erythroblasts co-expressing Spi-1 and the wild-type mouse EpoR showed that differentiation arrest and inhibition of apoptosis depended on specific cooperation between Spi-1 and EpoR(R129C). This cooperation was also required to induce the sustained proliferation of differentiation-blocked erythroblasts in response to ligand activation of the endogenous tyrosine kinase receptor c-Kit. These results show that Spi-1/PU.1 requires signals emanating from specific cytokine and growth factor receptors to affect the survival, proliferation and differentiation control of primary erythroblasts. They also suggest that the function of Spi-1/PU.1 in the late phase of Friend leukemia requires specific signaling from the gp55-modified EpoR generated during the early phase of the disease.

58 citations

Journal Article
TL;DR: It is shown that the nuclear PLC beta 1 isoform is down-regulated by tiazofurin (5 microM) treatment of Friend erythroleukemia cells as shown by both Western blot and Northern blot analyses for PLCbeta 1 message.
Abstract: Previous investigations have demonstrated the presence of conventional lipid kinases and phospholipase C (PLC) activities in nuclei of Friend erythroleukemia cells. Moreover, when Friend erythroleukemia cells are treated for 96 h with the antitumor drug tiazofurin, the induction of erythroid differentiation is accompanied by changes in amounts of both phosphatidylinositol and phosphatidylinositol 4,5-bisphosphate due to the inhibition of an uncharacterized nuclear PLC activity. Here, we show that the nuclear PLC beta 1 isoform is down-regulated by tiazofurin (5 microM) treatment of Friend erythroleukemia cells as shown by both Western blot and Northern blot analyses for PLC beta 1 message. This indicates that PLC beta 1 down-regulation is tightly linked with erythroid differentiation of Friend erythroleukemia cells and that the autonomous nuclear signaling via inositol lipid cycle can be controlled by the antitumor drug tiazofurin.

51 citations

Journal Article
TL;DR: Cells generated in a secondary response in vitro were not only cytotoxic in vitro and effective in tumor neutralization, but were also curative in immunotherapy of an early leukemia and in chemoimmunotherapy of a advanced leukemia.
Abstract: The aim of our study was to induce in vitro a secondary response to a C57BL/6 Friend leukemia (FBL-3) by C57BL/6 lymphoid cells, to document their enhanced anti-tumor cytotoxicity in vitro and to study their anti-tumor effect in vivo by tumor neutralization (Winn assay) and tumor therapy of progressive FBL-3 in C57BL/6 mice. Spleen cells (Ci) from mice immunized once in vivo with FBL-3 were cultured for 5 days with either x-irradiated FBL-3 (CiFx), C57BL/6 spleen cells (CiCx), BALB/c spleen cells (CiBx) or without any x-irradiated cells (Ci-cult.) and their activity subsequently was assayed in vitro and in vivo . CiFx cells were markedly more cytotoxic in vitro by the 51 Cr release assay than were CiCx or CiBx and were most effective in tumor neutralization (Winn assay). For adoptive immunotherapy, mice given lethal (10 4 ) FBL-3 i.p. on day 0 received the cultured spleen cells on day 1. Treatment with 5 × 10 6 CiFx cured 14 of 14 mice whereas 19 of 20 mice given 5 × 10 6 CiCx or CiBx died with tumor. For adoptive chemoimmunotherapy of advanced leukemia, mice were given 10 7 FBL-3 i.p. on day 0. On day 5, they received cyclophosphamide (CY) plus cultured spleen cells. Untreated mice died by day 14. CY alone prolonged survival but all mice died within 4 weeks. Treatment with CY plus 5 × 10 6 Ci-cult. or CiBx was no more effective than CY alone—40 of 40 mice died with tumor. However, CY plus 5 × 10 6 CiFx cured 16 of 22 mice. Thus, cells generated in a secondary response in vitro were not only cytotoxic in vitro and effective in tumor neutralization, but were also curative in immunotherapy of an early leukemia and in chemoimmunotherapy of an advanced leukemia.

50 citations

Journal Article
01 Jan 1990-Leukemia
TL;DR: Results indicate that Spi-1 gene activation is a general feature in the malignant proerythroblastic transformation which occurs in mice infected with Friend and Rauscher viruses.
Abstract: The Friend viruses, like the Rauscher virus, cause murine acute erythroleukemias which evolve in a similar multistep process. In previous studies it has been described that the late malignant proerythroblastic transformation induced by the polycythemia-inducing strain of Friend spleen focus-forming virus (SFFVP) is correlated with Spi-1 oncogene activation by insertional mutagenesis. In this paper we report that Spi-1 genomic rearrangements were also observed in 90% of tumors induced by the anemia-inducing strain of Friend spleen focus-forming virus (SFFVA) and in all Rauscher-induced tumors analyzed. SFFVA and Rauscher proviral insertions occurred in the viral integration cluster previously characterized in SFFVP-induced tumors. The Spi-1 1.4-Kb messenger RNA was found highly expressed in all SFFVA and Rauscher-induced malignant cells as compared to normal tissues. The nucleotide sequence of Spi-1 cDNA isolated from a library constructed from SFFVA-induced tumor cells revealed no difference between the Spi-1 gene transcripts expressed in both SFFVP and SFFVA-induced leukemic cells. These results indicate that Spi-1 gene activation is a general feature in the malignant proerythroblastic transformation which occurs in mice infected with Friend and Rauscher viruses.

49 citations

Journal Article
TL;DR: NMR spectroscopy can be a useful means to monitor the level of some phospholipid precursors and/or derivatives as early markers of therapeutic efficacy in intact neoplastic tissues in murine tumors injected with recombinant murine tumor necrosis factor (TNF).
Abstract: The alterations induced on the pool sizes of five phospholipid metabolites, glycerol 3-phosphorycholine, glycerol 3-phosphorylethanolamine, phosphorylcholine, sn-glycerol 3-phosphate, and choline were studied by nuclear magnetic resonance (NMR) spectroscopy in murine tumors injected with recombinant murine tumor necrosis factor (TNF). Solid tumors were obtained by s.c. injection of either Friend leukemia cells (clones 3C1-8 and 745) in DBA/2 mice or murine fibrosarcoma cells (HeN4) in C3H/HeN mice. After tumor nodules had developed, TNF or bovine serum albumin was injected intratumorally. Treatment of both tumors with TNF resulted in a marked inhibition of tumor growth. 31P-NMR analyses of Friend leukemia cell tumors (and tissue extracts), 6 h after injection of TNF, showed: (a) a 1.5- to 3.5-fold decrease in the pool sizes of glycerol 3-phosphorylcholine and glycerol 3-phosphorylethanolamine; (b) a 7- to 8-fold increase of sn-glycerol 3-phosphate; (c) a 2- to 3.5-fold decrease of phosphorylcholine; (d) an alkaline shift (0.2 units) in intratumoral pH. Similar metabolic alterations occurred in TNF-treated HeN4 fibrosarcoma. 1H-NMR analyses of Friend leukemia cell tumor extracts also indicated, 6 h after tumor injection with TNF: (a) elevated choline levels (9X); (b) a 19-fold increase in the ratio [choline]/[phosporylcholine]; (c) elevated (1.4X) levels of lactic acid; and (d) a 1.6-fold decrease in the [taurine]/[glycine] ratio. The results are interpreted in the light of possible alterations in the activity of enzymes controlling the de novo biosynthesis and catabolism of phospholipids. We concluded that NMR spectroscopy can be a useful means to monitor the level of some phospholipid precursors and/or derivatives as early markers of therapeutic efficacy in intact neoplastic tissues.

49 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20213
20192
20161
20151
20143
20121