The influence of Rauscher Leukemia Virus (R-MuLV) on the differentiation of red blood cells in BALB/c mice

Abstract

The influence of Rauscher Leukemia Virus infection of BALB/c mice on the differentiation of red blood cells has been investigated. Twenty-one days after infection, the total number of red blood cells in the spleen is increased 20 times in contrast to the bone marrow which is largely unaffected. The cellular composition of these hemopoietic organs has been analysed using a number of markers of erythroid maturation, i.e. heme and hemoglobin synthesis and the presence of globin messenger RNAs. These studies show that most of the blasts present in leukemic spleens are immature as judged by morphological criteria and do not contain globin mRNA, whereas the more mature blasts contain globin mRNA as determined autoradiographically by in situ hybridization to globin cDNA. The number of mature blasts, comprising about one-third of the immature ones, is both in absolute terms and per mg tissue higher than in control spleens. Pulse labelling with 59Fe shows, that heme and hemoglobin synthesis takes place in leukemic spleens. The rate of heme synthesis in leukemic spleens, as judged by short-term incorporation of 59Fe and 14C-glycine is intermediate between the values for spleens from anemic and control animals. After a pulse, labelled 59Fe is first bound to non-hemoglobin proteins. After a chase, this protein-bound 59Fe is transferred to hemoglobin as erythroid differentiation occurs in spleens of normal and anemic mice. However, this transfer of 59Fe to hemoglobin does not occur in leukemic spleen cells during a pulse/chase in vivo. These results could mean that these immature blasts die or that the maturation is inhibited in the enlarged spleens, whereas only a minor portion differentiates in smaller basophilic erythroblasts, which mature into reticulocytes.