MARROW FAILURE: VIRUS-INDUCED DISEASE

再生障碍性贫血是一种由多种原因引起的复杂疾病。在

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.