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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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Journal ArticleDOI
TL;DR: The data identify a mechanism for development of the familial thrombocytopenia THC2 that is related to abnormal MAPK signaling and ERK inhibition completely rescued the in vitro proplatelet formation defect.
Abstract: Point mutations in the 5′ UTR of ankyrin repeat domain 26 (ANKRD26) are associated with familial thrombocytopenia 2 (THC2) and a predisposition to leukemia. Here, we identified underlying mechanisms of ANKRD26-associated thrombocytopenia. Using megakaryocytes (MK) isolated from THC2 patients and healthy subjects, we demonstrated that THC2-associated mutations in the 5′ UTR of ANKRD26 resulted in loss of runt-related transcription factor 1 (RUNX1) and friend leukemia integration 1 transcription factor (FLI1) binding. RUNX1 and FLI1 binding at the 5′ UTR from healthy subjects led to ANKRD26 silencing during the late stages of megakaryopoiesis and blood platelet development. We showed that persistent ANKRD26 expression in isolated MKs increased signaling via the thrombopoietin/myeloproliferative leukemia virus oncogene (MPL) pathway and impaired proplatelet formation by MKs. Importantly, we demonstrated that ERK inhibition completely rescued the in vitro proplatelet formation defect. Our data identify a mechanism for development of the familial thrombocytopenia THC2 that is related to abnormal MAPK signaling.

156 citations

Journal ArticleDOI
07 Nov 1986-Science
TL;DR: Mice inoculated with live recombinant vaccinia virus had an envelope-specific T-cell proliferative response and, after challenge with Friend virus complex, developed neutralizing antibody and cytotoxic T cells (CTL) and were protected against leukemia.
Abstract: The current prevalence of the acquired immune deficiency syndrome in humans has provoked renewed interest in methods of protective immunization against retrovirus-induced diseases. In this study, a vaccinia-retrovirus recombinant vector was constructed to study mechanisms of immune protection against Friend virus leukemia in mice. The envelope (env) gene from Friend murine leukemia virus (F-MuLV) was inserted into the genome of a vaccinia virus expression vector. Infected cells synthesized gp85, the glycosylated primary product of the env gene. Processing to gp70 and p15E, and cell surface localization, were similar to that occurring in cells infected with F-MuLV. Mice inoculated with live recombinant vaccinia virus had an envelope-specific T-cell proliferative response and, after challenge with Friend virus complex, developed neutralizing antibody and cytotoxic T cells (CTL) and were protected against leukemia. In contrast, unimmunized and control groups developed a delayed neutralizing antibody response, but no detectable CTL, and succumbed to leukemia. Genes of the major histocompatibility complex influenced protection induced by the vaccinia recombinant but not that induced by attenuated N-tropic Friend virus.

142 citations

Journal ArticleDOI
TL;DR: Genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45, providing direct evidence that NF- E2 gene is essential for globin transcription and suggesting that perturbation in expression of this transcription factor may contribute to erystroleukemia progression.
Abstract: Activation of either Fli-1 or Spi-1 members of the ets family of transcription factors as a result of retroviral insertion and mutational inactivation of the p53 tumor suppressor gene play essential roles in the multistage erythroleukemias induced in mice by various strains of Friend virus. We have previously identified another common site for provirus integration, designated Fli-2 (Friend leukemia integration 2), in some erythroleukemia clones induced either by Friend murine leukemia virus (F-MuLV) or by the polycythemia-inducing strain of Friend virus complex (FV-P). Here we show that genomic sequences adjacent to Fli-2 correspond to the coding region of the erythroid-specific DNA binding protein NF-E2 p45. In one erythroleukemia cell line the expression of NF-E2 p45 is undetectable due to proviral integration in one allele and loss of the other allele. The complete loss of NF-E2 p45 in this cell line is associated with a drastic reduction in expression of the alpha- and beta-globin genes that were partially restored by reintroduction of the NF-E2 p45 gene. Taken together, these results provide direct evidence that NF-E2 gene is essential for globin transcription and suggest that perturbation in expression of this transcription factor may contribute to erythroleukemia progression.

132 citations

Journal ArticleDOI
TL;DR: SFFV appears to be unique in its ability to abrogate the factor dependence of Epo-dependent HCD-57 cells, since infection of these cells with retroviruses carrying a variety of different oncogenes had no effect.
Abstract: Erythroid cells from mice infected with the polycythemia-inducing strain of Friend spleen focus-forming virus (SFFVP), unlike normal erythroid cells, can proliferate and differentiate in apparent absence of the erythroid hormone erythropoietin (Epo). The unique envelope glycoprotein encoded by SFFV has been shown to be responsible for this biological effect. The recent isolation of an Epo-dependent erythroleukemia cell line, HCD-57, derived from a mouse infected at birth with Friend murine leukemia virus, afforded us the opportunity to study the direct effect of SFFVP on a homogeneous population of factor-dependent cells. The introduction of SFFVP in complex with various helper viruses into these Epo-dependent cells efficiently and reproducibly gave rise to lines which expressed high levels of SFFV and were factor independent. SFFV appears to be unique in its ability to abrogate the factor dependence of Epo-dependent HCD-57 cells, since infection of these cells with retroviruses carrying a variety of different oncogenes had no effect. The induction of Epo independence by SFFV does not appear to involve a classical autocrine mechanism, since there is no evidence that the factor-independent cells synthesize or secrete Epo or depend on it for their growth. However, the SFFV-infected, factor-independent cells had significantly fewer receptors available for binding Epo than their factor-dependent counterparts had, raising the possibility that the induction of factor independence by the virus may be due to the interaction of an SFFV-encoded protein with the Epo receptor.

124 citations

Journal ArticleDOI
TL;DR: Results indicate that the absolute configuration and the presence of the hydroxamate group of trichostatin A are essential for its biological activity.
Abstract: Biological activities of four chemically synthesized trichostatin-related compounds, (R)-trichostatin A, (S)-trichostatin A, (R)-trichostatic acid, and (S)-trichostatic acid, were investigated. Assays of differentiation-inducing activity in Friend leukemia cells and G2-arresting activity in the cell cycle of normal rat fibroblast cells were used as monitoring systems for comparing the bioactivities of these compounds. The results clearly showed that both of the enantiomers of trichostatic acid had no activity in both the assay systems. In the case of (S)-trichostatin A, the antipode of naturally occurring trichostatin A, 50% effective concentrations were determined to be 50-70-fold higher than those of (R)-trichostatin A. The relationship between this ratio and the value of enantiomeric excess strongly suggests that (S)-trichostatin A is also biologically inactive. These results indicate that the absolute configuration and the presence of the hydroxamate group of trichostatin A are essential for its biological activity.

121 citations


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