MARROW FAILURE: VIRUS-INDUCED DISEASE

男性再生障碍性贫血是一种多病因的复杂疾病。其中 它们是电离辐射等物质对干细胞的直接损伤， 免疫介导的损伤，对祖细胞的直接病毒效应， 和髓系干细胞的肿瘤转化。为了更好地 了解了再生障碍性贫血的一些机制，我们已经开发出一种 猫白血病病毒(FeLV)致骨髓衰竭(纯)动物模型 红细胞再生障碍性贫血)。我们故意感染了免疫抑制的动物 并产生了严重的贫血。评估FeLV诱导的水平 在骨髓衰竭的情况下，我们已经开发了各种克隆检测方法 培养中的造血祖细胞。能够检测到肿瘤 转化和骨髓衰竭由一种 肿瘤性髓系或淋巴系细胞群，我们已经培育出了国内和 野生型(Geoffroy)猫具有不同的G-6-PD酶类型。F1 女性是稳定的G-6-PD杂合子，我们已经证明 X染色体失活。通过体外试验和体内试验相结合 活体研究，我们将检查病毒对造血的影响 祖细胞生长，辅助细胞参与的可能性 在骨髓抑制的过程中，判断是否有骨髓衰竭 肿瘤髓系干细胞克隆扩增的结果 淋巴样肿瘤。

Aplastic anemia in man is a complex disorder of multiple causes. Among them are direct stem cell damage by agents such as ionizing radiation, immunologically-mediated damage, direct viral effects on progenitor cells, and neoplastic transformation of the myeloid stem cell. To better understand some of the mechanisms involved in aplasia, we have developed an animal model of feline leukemia virus (FeLV)-induced marrow failure (pure red cell aplasia). We have deliberately infected immmunosuppressed animals and produced severe anemia. To assess the level at which FeLV induces marrow failure, we have developed clonogenic assays for various hematopoietic progenitor cells in culture. To be able to detect neoplastic transformation and the possibility that marrow failure results from a neoplastic myeloid or lymphoid cell population, we have bred domestic and wild type (Geoffroy) cats having different G-6-PD enzyme types. The F1 females are stable G-6-PD heterozygotes and we have demonstrated X-chromosome inactivation. Through a combination of both in vitro and in vivo studies, we will examine the effects of virus on hematopoietic progenitor cell growth, the possibility that auxiliary cells are involved in the process of marrow suppression, and determine whether marrow failure results from the clonal expansion of a neoplastic myeloid stem cell or a lymphoid neoplasm.