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: 3916361
• 负责人: S K RUSCETTI
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 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/3916361
• 关键词: Friend virus; Retroviridae disease; cell differentiation; cell growth regulation; erythroid stem cell; erythroleukemia; erythropoietin; gene expression; genetic mapping; glycoproteins; laboratory mouse; molecular cloning; molecular oncology; neoplasm /cancer genetics; nucleic acid sequence; oncogenes; oncogenic virus; spleen; tissue /cell culture; viral leukemia; viral leukemogenesis; virus envelope; virus genetics; virus protein; virus replication

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. Investigations on the acute erythroleukemias-inducing spleen focus- forming virus (SFFV) have concentrated on understanding how this virus alters the growth and differentiation of erythroid cells. Erythroid cells form SFFV-infected mice differ form normal erythroid cells in that they can proliferate and differentiate in the apparent absence of the erythroid hormone erythropoietin (Epo). The unique envelope gene carried by SFFV has been shown to be responsible for the biological effects of the virus. Our recent results indicate that SFFV-infected erythroid cells neither secrete an erythroid growth factor that stimulates their growth in an autocrine-like manner nor make detectable levels of Epo-specific mRNA. In addition, SFFV-infected erythroid cells do not differ from their normal counterparts in the number, affinity or size of their Epo receptors. Thus, SFFV is not altering the hormonal requirements of erythroid cells at the level of Epo or its receptor. Studies on the genetics of susceptibility to erythroleukemia induced by Friend MuLV are concentrating on a gene previously identified on chromosome 5, at or near the Rmcf locus, that encodes a viral enveloe glycoprotein related to that of mink cell focus- inducing viruses. RNA transcripts have been identified in tissues from resistant mice that may encode this envelope glycoprotein and cDNA cloning of this putative resistance gene is in progress.

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