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MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES

MOLECULAR BASIS FOR THE ACUTE ERYTHROLEUKEMIAS INDUCED BY MURINE RETROVIRUSES
鼠逆转录病毒引起的急性红白血病的分子基础
批准号:
3874799
负责人:
S K RUSCETTI
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:

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中文摘要
翻译
研究的目的是试图了解 小鼠白血病病毒诱导红细胞转化, 为什么某些品系的小鼠对一个或多个阶段的 恶性过程 急性红白血病脾灶形成病毒的研究 (SFFV)已经集中精力了解这种病毒如何消除 促红细胞生成素(Epo)的需求。中存在的序列 发现病毒包膜蛋白的跨膜结构域是 这对于使细胞不依赖于Epo至关重要。除了造成 在小鼠红白血病中,SFFV也可以有效地和可重复地使 不依赖于促红细胞生成素的细胞系因子。的诱导 因子独立性似乎不涉及经典的自分泌 机制,但可能是由于SFFV编码的蛋白质的相互作用 与Epo受体有关。在其他研究中,研究表明, Akv辅助病毒通过其将SFFV引入红系靶细胞 是由于其包膜基因的304 bp区域。 致红白血病易感性的遗传学研究 Friend MuLV已经表明,来自携带Rmcf(r)基因座的小鼠的DNA 含有一种独特的前病毒,与一种改良的多变病毒有关, 不存在于Rmcf小鼠的DNA中。在其他研究中, Rmcf基因不影响小鼠对胸腺细胞的易感性, Moloney MuLV诱导的淋巴瘤。 关于ME 26病毒的作用的研究,ME 26病毒含有myb和 ets癌基因的研究表明, 线可以很容易地和可重复地从脾脏的 ME 26感染小鼠。Epo依赖性细胞在形态上是不同的 来自SFFV和F-MuLV诱导的红白血病细胞系, 红系前体细胞或干细胞。
英文摘要
Studies have been aimed at trying to understand the mechanisms by which murine leukemia viruses induce erythroid transformation and to understand why some strains of mice are resistant to one or more stages of the malignant process. Studies on the acute erythroleukemia-inducing spleen focus-forming virus (SFFV) have concentrated on understanding how this virus abrogates the erythropoietin (Epo) requirement of erythroid cells. Sequences present in the transmembrane domain of the viral envelope protein were found to be essential for rendering the cells Epo-independent. In addition to causing erythroleukemia in mice, SFFV also can efficiently and reproducibly render an erythropoietin-dependent cell line factor-independent. The induction of factor independence does not appear to involve a classical autocrine mechanism, but may be due to the interaction of an SFFV-encoded protein with the Epo receptor. In other studies, it was shown that the inefficiency with which the Akv helper virus introduces SFFV into erythroid target cells is due to a 304 bp region of its envelope gene. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV have shown that DNA from mice carrying the Rmcf(r) locus contain a unique provirus, related to a modified polytropic virus, that is not present in the DNA from Rmcf(s) mice. In other studies, it was shown that the Rmcf gene does not effect susceptibility of mice to thymic lymphoma induced by Moloney MuLV. Studies on the effects of the ME26 virus, which contains both the myb and ets oncogenes, on hematopoietic cells have shown that Epo-dependent cell lines can easily and reproducibly be derived from the spleens of ME26-infected mice. The Epo-dependent cells are morphologically distinct from SFFV and F-MuLV-induced erythroleukemia lines and resemble early erythroid precursors or stem cells.
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