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: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3874799
• 关键词: Friend leukemia; erythroid stem cell; erythroleukemia; erythropoietin; helper virus; hormone receptor; hormone related neoplasm /cancer; laboratory mouse; lymphoma; molecular oncology; provirus; viral leukemogenesis; virus envelope; virus genetics; virus protein

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.

研究的目的是试图了解 小鼠白血病病毒诱导红系转化和理解 为什么某些品系的小鼠对一个或多个阶段的 恶性过程。 急性红白血病诱发的脾肿瘤形成病毒的研究 (SFFV)专注于了解这种病毒如何废除 红系细胞的促红细胞生成素(EPO)需求。中存在的序列 病毒包膜蛋白的跨膜区被发现是 使细胞不依赖EPO所必需的。除了引起 在小鼠的红白血病中，SFFV也可以高效和可重复性地呈现 一种不依赖于因子的促红细胞生成素依赖细胞系。的归纳 要素独立性似乎并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 与促红细胞生成素受体有关。在其他研究中，研究表明，效率低下 AkV辅助病毒通过该病毒将SFFV引入红系靶细胞 是由于其包膜基因的304个碱基对所致。 慢性粒细胞白血病易感性的遗传学研究 朋友MuLV表明，携带Rmcf(R)基因座的小鼠的DNA 包含一种独特的前病毒，与一种经修改的多嗜性病毒有关，即 不存在于Rmcf(S)小鼠的DNA中。在其他研究中，它被证明 Rmcf基因不影响小鼠对胸腺的易感性 Moloney MuLV诱发的淋巴瘤。 同时含有MYB和MYB的ME26病毒的作用研究 Ets癌基因，在造血细胞上已显示EPO依赖细胞 线条可以很容易和可重复地从脾中提取出来 感染ME26的小鼠。EPO依赖的细胞在形态上是不同的。 来自SFFV和F-MuLV诱导的红白血病株，并与早期相似 红系前体或干细胞。